Process for diastereoselective conversion of chiral imines

ABSTRACT

Diastereoselective conversion of chiral imines of the formula I to amines of the formula II 
     
       
         
         
             
             
         
       
     
     where the R 1  to R 4  radicals are each as defined in the description and R 1  and R 2  are different than one another, by converting the imine of the formula I in the presence of hydrogen and a heterogeneous copper-containing catalyst.

The present invention relates to a process for diastereoselectiveconversion of chiral imines of the formula I to amines of the formula II

-   where-   R¹, R² are each C₁-C₆-alkyl, C₃-C₆-cycloalkyl, C₂-C₆-alkenyl,    C₂-C₆-alkynyl, C₂-C₆-haloalkenyl, C₂-C₆-haloalkynyl,    C₁-C₆-alkoxycarbonyl, C₃-C₆-alkenyloxycarbonyl,    C₃-C₆-alkynyloxycarbonyl, aminocarbonyl, C₁-C₆-alkylaminocarbonyl,    C₃-C₆-alkenylaminocarbonyl, C₃-C₆-alkynylaminocarbonyl,    C₁-C₆-alkylsulfonyl-aminocarbonyl, di(C₁-C₆-alkyl)aminocarbonyl,    N-(C₃-C₆-alkenyl)-N-(C₁-C₆-alkyl)aminocarbonyl,    N-(C₃-C₆-alkynyl)-N-(C₁-C₆-alkyl)aminocarbonyl,    N-(C₁-C₆-alkoxy)-N-(C₁-C₆-alkyl)aminocarbonyl,    N-(C₃-C₆-alkenyl)-N-(C₁-C₆-alkoxy)aminocarbonyl,    N-(C₃-C₆-alkynyl)-N-(C₁-C₆-alkoxy)aminocarbonyl,    (C₁-C₆-alkyl)aminothiocarbonyl, di(C₁-C₆-alkyl)aminothiocarbonyl or    C₁-C₆-alkylcarbonyl-C₁-C₆-alkyl,    -   where the alkyl, cycloalkyl and alkoxy radicals mentioned may be        partially or fully halogenated and/or may bear from one to three        of the following groups: cyano, hydroxyl, C₁-C₄-alkyl,        C₃-C₆-cycloalkyl, C₁-C₆-alkoxy-C₁-C₄-alkyl,        C₁-C₄-alkoxy-C₁-C₄-alkoxy-C₁-C₄-alkyl, C₁-C₄-alkoxy,        C₁-C₄-alkylthio, amino, C₁-C₄-alkylamino, di(C₁-C₄-alkyl)amino,        C₁-C₄-alkylcarbonylamino, hydroxycarbonyl, C₁-C₄-alkoxycarbonyl,        aminocarbonyl, C₁-C₄-alkylaminocarbonyl,        di(C₁-C₄-alkyl)amino-carbonyl or C₁-C₄-alkylcarbonyloxy;    -   aryl, aryl-C₁-C₄-alkyl, aryl-C₂-C₄-alkenyl, aryl-C₂-C₄-alkynyl,        aryl-C₁-C₄-haloalkyl, aryl-C₂-C₄-haloalkenyl,        aryl-C₃-C₄-haloalkynyl, aryl-C₁-C₄-hydroxyalkyl,        arylcarbonyl-C₁-C₄-alkyl, aryl-C₁-C₄-alkylcarbonyl-C₁-C₄-alkyl,        arylcarbonyloxy-C₁-C₄-alkyl, aryloxycarbonyl-C₁-C₄-alkyl,        aryloxy-C₁-C₄-alkyl, arylamino-C₁-C₄-alkyl,        arylthio-C₁-C₄-alkyl, arylsulfinyl-C₁-C₄-alkyl,        arylsulfonyl-C₁-C₄-alkyl, heterocyclyl,        heterocyclyl-C₁-C₄-alkyl, heterocyclyl-C₂-C₄-alkenyl,        heterocyclyl-C₂-C₄-alkynyl, heterocyclyl-C₁-C₄-haloalkyl,        heterocyclyl-C₂-C₄-haloalkenyl, heterocyclyl-C₃-C₄-haloalkynyl,        heterocyclyl-C₁-C₄-hydroxyalkyl,        heterocyclylcarbonyl-C₁-C₄-alkyl,        heterocyclyl-C₁-C₄-alkyl-carbonyl-C₁-C₄-alkyl,        heterocyclylcarbonyloxy-C₁-C₄-alkyl,        heterocyclyloxycarbonyl-C₁-C₄-alkyl,        heterocyclyloxy-C₁-C₄-alkyl, heterocyclylamino-C₁-C₄-alkyl,        heterocyclylthio-C₁-C₄-alkyl, heterocyclylsulfinyl-C₁-C₄-alkyl,        heterocyclylsulfonyl-C₁-C₄-alkyl, where the aforementioned        radicals may be partially or fully halogenated and/or may bear        from one to three radicals from the group of cyano, nitro,        C₁-C₆-alkyl, C₁-C₆-haloalkyl, hydroxyl, C₁-C₆-hydroxyalkyl,        hydroxycarbonyl-C₁-C₆-alkyl, C₁-C₆-alkoxycarbonyl-C₁-C₆-alkyl,        C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, hydroxycarbonyl,        C₁-C₆-alkoxycarbonyl, aminocarbonyl, (C₁-C₆-alkyl)aminocarbonyl,        di(C₁-C₆-alkyl)aminocarbonyl, hydroxycarbonyl-C₁-C₆-alkoxy,        C₁-C₆-alkoxycarbonyl-C₁-C₆-alkoxy, amino, C₁-C₆-alkylamino,        di(C₁-C₆-alkyl)amino, C₁-C₆-alkylsulfonylamino,        C₁-C₆-haloalkylsulfonylamino, (C₁-C₆-alkyl)aminocarbonylamino,        di(C₁-C₆-alkyl)-aminocarbonylamino, aryl and aryl(C₁-C₆-alkyl);    -   where the R¹ and R² radicals are different than one another;-   R³ is C₁-C₆-alkyl;-   R⁴ is aryl which may be partially or fully halogenated and/or may    bear from one to three radicals from the group of cyano, nitro,    C₁-C₆-alkyl, C₁-C₆-haloalkyl, hydroxyl, C₁-C₆-hydroxyalkyl,    C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, hydroxycarbonyl,    C₁-C₆-alkoxycarbonyl, C₁-C₆-alkylamino, di(C₁-C₆-alkyl)amino, aryl    and aryl(C₁-C₆-alkyl);-   and-   * represents the S or R configuration, and-   ** represents the S and/or R configuration;    by converting the imine of the formula I in the presence of hydrogen    and a heterogeneous copper-containing catalyst.

There are frequent descriptions in the literature of thediastereoselective conversion of chiral imines, the substituent on theimino nitrogen bearing the chirality, in the presence of hydrogen, togive corresponding amines in the presence of platinum oxide, palladiumon carbon, etc. EP 443 606 describes the reaction of optically active1-phenylethylamine with 4-(4-methoxyphenyl)-2-butanone and subsequenthydrogenation with hydrogen in the presence of palladium on carbon(Example 4).

It is also known that diastereoselective hydrogenations of imines, thesubstituent on the imino nitrogen bearing the chirality, tocorresponding amines can be carried out in the presence of nickelskeletal catalysts (Raney™ type). EP 443 606 likewise describes thereaction of optically active 1-phenylethylamine with4-(4-methoxyphenyl)-2-butanone and subsequent hydrogenation withhydrogen in the presence of Raney nickel (Example 1B).

A disadvantage in these processes is the sometimes poordiastereoselectivity of the hydrogenation and/or the difficulty inremoving the nickel skeletal catalyst (Raney™ type).

WO 01/09080 further describes a process for cis-selective preparation ofcyclic amines of the sertraline type, by reacting a cyclic ketone withan achiral amine to the corresponding imine and the latter is thensubjected to a catalytic hydrogenation in the presence of acopper-containing catalyst, especially copper chromite.

It was an object of the present invention to provide a generallyapplicable process for diastereoselective conversion of chiral imines,the substituent on the imino nitrogen thus bearing the chirality, tocorresponding amines, which does not have the abovementioneddisadvantages.

In accordance with the above object, it has been found that thediastereoselectivity and/or the conversion in the reaction of chiralimines of the formula I to amines of the formula II can be improved whenheterogeneous catalysts which comprise nickel, cobalt and/or zinc, andwhich additionally comprise copper, are used.

The process according to the invention proceeds from chiral imines ofthe formula I, wherein the substituent on the imino nitrogen (—C*HR³R⁴)is either in the R or S configuration.

The reaction is effected generally in a solvent. However, it is alsopossible to carry out the reaction in substance, especially when theimine of the formula I is liquid at the reaction temperature. Thesolvents used are solvents which are inert under the reactionconditions, such as alcohols, for example methanol, ethanol, n-propanol,isopropanol, cyclopentanol, cyclohexanol, ethylene glycol, propyleneglycol etc., aromatic hydrocarbons, for example benzene, toluene,ethylbenzene, xylene etc., chlorinated hydrocarbons, for examplemethylene chloride, chloroform, carbon tetrachloride,1,2-dichloromethane, chlorobenzene etc., ethers, for example diethylether, methyl tert-butyl ether, ethylene glycol dimethyl ether,tetrahydrofuran, dioxane, dipolar aprotic solvents, for exampleN-methylpyrrolidone, dimethyl sulfoxide, sulfolane, dimethylformamide,dimethylacetamide etc., or mixtures thereof. Preference is given toperforming the reaction in an alcohol, such as methanol, ethanol,n-propanol, isopropanol, cyclopentanol, cyclohexanol, ethylene glycol,propylene glycol etc., preferably methanol, ethanol or isopropanol, oran aromatic hydrocarbon, such as benzene, toluene, ethylbenzene, xyleneetc., preferably toluene or ethylbenzene, or mixtures thereof.

The weight ratio of imine to solvent may vary within wide ranges.Typically, it is within the range from 0.01% to 99%, preferably from0.1% to 95%, especially from 1% to 90%, more preferably from 10% to 70%,exceptionally preferably from 15-60%.

Typically, the reaction is performed at a temperature from roomtemperature to reflux temperature of the reaction mixture, generallyfrom room temperature to 200° C.

In general, the reaction is performed at a pressure of from standardpressure to 200 bar, preferably from 40 to 150 bar, especially from 50to 100 bar. It is possible to increase the pressure up to the desiredpressure in stages or else continuously.

The hydrogen or the hydrogen of the hydrogen-comprising gas stream canbe reacted fully or partly. In the latter case, it may be advantageousfrom case to case to recycle this gas stream partly or fully, or torecirculate it. In the case that the copper-containing catalyst used isactivated before the reaction, this gas stream can also be used for thispurpose.

Typically, hydrogen of technical grade quality is used. The hydrogencan, though, also be used in the form of a hydrogen-comprising gas, i.e.as an admixture of an inert gas, such as nitrogen, helium, neon, argonor carbon dioxide, preferably nitrogen or argon.

The inventive reaction is carried out in the presence of a heterogeneouscopper-containing catalyst.

This heterogeneous copper-containing catalyst preferably comprises,based on the total weight of the catalyst,

-   0.1-95% by weight of copper;-   0.1-85% by weight of at least one metal selected from the group of    nickel, cobalt and zinc;-   0-15% by weight of at least one promoter selected from the group of    iron, rhodium, ruthenium, palladium, platinum, iridium, osmium,    silver, gold, molybdenum, tungsten, rhenium, cadmium, lead,    manganese, tin, chromium, lithium, sodium, potassium, cesium,    magnesium, barium, phosphorus, arsenic, antimony, bismuth, selenium    and tellurium;    where the sum of the percentages by weight does not exceed 100%.

In general, the heterogeneous copper-containing catalyst comprises asupport material. Useful support materials include carbon, for exampleactivated carbon, graphite or carbon black, or a porous metal oxide.Examples of suitable porous metal oxides are aluminum oxide, silicondioxide, aluminosilicates, titanium dioxide, zirconium dioxide,magnesium oxide or mixtures thereof, preferably aluminum oxide, titaniumdioxide or zirconium dioxide. However, it is also possible to use, assupport materials, aluminum phosphates, mullites, kieselguhr, bauxitesand potassium aluminates.

In particular, the total weight of the abovementioned catalyticallyactive metals and if appropriate promoters in the heterogeneouscopper-containing catalyst, based on its total weight, is at most 95% byweight, preferably at most 90% by weight.

In a further embodiment, this heterogeneous copper-containing catalystis an unsupported catalyst.

In one embodiment, this heterogeneous copper-containing catalystcomprises, based on the total weight of the catalyst

-   1-90% by weight of copper;-   0.1-80% by weight of at least one metal selected from the group of    nickel, cobalt and zinc;-   0-15% by weight of at least one promoter selected from the group of    iron, rhodium, ruthenium, palladium, platinum, iridium, osmium,    silver, gold, molybdenum, tungsten, rhenium, cadmium, lead,    manganese, tin, chromium, lithium, sodium, potassium, cesium,    magnesium, barium, phosphorus, arsenic, antimony, bismuth, selenium    and tellurium.

In particular, this heterogeneous copper-containing catalyst comprises,based on the total weight of the catalyst,

-   2-85% by weight of copper;-   0.1-80% by weight of at least one metal selected from the group of    nickel, cobalt and zinc;-   0-15% by weight of at least one promoter selected from the group of    iron, rhodium, ruthenium, palladium, platinum, iridium, osmium,    silver, gold, molybdenum, tungsten, rhenium, cadmium, lead,    manganese, tin, chromium, lithium, sodium, potassium, cesium,    magnesium, barium, phosphorus, arsenic, antimony, bismuth, selenium    and tellurium.

In a further embodiment, this heterogeneous copper-containing catalystcomprises, based on the total weight of the catalyst,

-   2-50% by weight of copper;-   0-30% by weight of at least one metal selected from the group of    nickel and cobalt;-   0.5-50% by weight of zinc;-   0-5% by weight of at least one promoter selected from the group of    iron, rhodium, ruthenium, palladium, platinum, iridium, osmium,    silver, gold, molybdenum, tungsten, rhenium, cadmium, lead,    manganese, tin, chromium, lithium, sodium, potassium, cesium,    magnesium, barium, phosphorus, arsenic, antimony, bismuth, selenium    and tellurium.

This heterogeneous copper-containing catalyst preferably comprises,based on the total weight of the catalyst,

-   5-40% by weight of copper;-   0-30% by weight of at least one metal selected from the group of    nickel and cobalt;-   5-50% by weight of zinc;-   0-5% by weight of at least one promoter selected from the group of    iron, rhodium, ruthenium, palladium, platinum, iridium, osmium,    silver, gold, molybdenum, tungsten, rhenium, cadmium, lead,    manganese, tin, chromium, lithium, sodium, potassium, cesium,    magnesium, barium, phosphorus, arsenic, antimony, bismuth, selenium    and tellurium.

In particular, this heterogeneous copper-containing catalyst comprises,based on the total weight of the catalyst,

-   10-35% by weight of copper;-   0-30% by weight of at least one metal selected from the group of    nickel and cobalt;-   10-45% by weight of zinc;-   0-5% by weight of at least one promoter selected from the group of    iron, rhodium, ruthenium, palladium, platinum, iridium, osmium,    silver, gold, molybdenum, tungsten, rhenium, cadmium, lead,    manganese, tin, chromium, lithium, sodium, potassium, cesium,    magnesium, barium, phosphorus, arsenic, antimony, bismuth, selenium    and tellurium.

This heterogeneous copper-containing catalyst more preferably comprises,based on the total weight of the catalyst,

-   10-35% by weight of copper;-   10-40% by weight of zinc;-   0-5% by weight of at least one promoter selected from the group of    iron, rhodium, ruthenium, palladium, platinum, iridium, osmium,    silver, gold, molybdenum, tungsten, rhenium, cadmium, lead,    manganese, tin, chromium, lithium, sodium, potassium, cesium,    magnesium, barium, phosphorus, arsenic, antimony, bismuth, selenium    and tellurium.

This copper-containing catalyst especially preferably comprises, ascatalytically active metals, only copper and zinc, especially in eachcase (but independently) from 5 to 50% by weight, more preferably from10 to 45% by weight, especially preferably from 20 to 40% by weight,based on the total weight of the catalyst. The support material ispreferably a porous metal oxide, especially aluminum oxide, titaniumdioxide or zirconium dioxide.

In a further embodiment, this heterogeneous copper-containing catalystcomprises, based on the total weight of the catalyst,

-   2-50% by weight of copper;-   0.1-70% by weight of nickel;-   0-30% by weight of at least one metal selected from the group of    cobalt and zinc;-   0-5% by weight of at least one promoter selected from the group of    iron, rhodium, ruthenium, palladium, platinum, iridium, osmium,    silver, gold, molybdenum, tungsten, rhenium, cadmium, lead,    manganese, tin, chromium, lithium, sodium, potassium, cesium,    magnesium, barium, phosphorus, arsenic, antimony, bismuth, selenium    and tellurium.

This heterogeneous copper-containing catalyst preferably comprises,based on the total weight of the catalyst,

-   2-40% by weight of copper;-   1-65% by weight of nickel;-   0-10% by weight of at least one metal selected from the group of    cobalt and zinc;-   0-5% by weight of at least one promoter selected from the group of    iron, rhodium, ruthenium, palladium, platinum, iridium, osmium,    silver, gold, molybdenum, tungsten, rhenium, cadmium, lead,    manganese, tin, chromium, lithium, sodium, potassium, cesium,    magnesium, barium, phosphorus, arsenic, antimony, bismuth, selenium    and tellurium.

In particular, this heterogeneous copper-containing catalyst comprises,based on the total weight of the catalyst,

-   2-25% by weight of copper;-   3-60% by weight of nickel;-   0-10% by weight of at least one metal selected from the group of    cobalt and zinc;-   0-5% by weight of at least one promoter selected from the group of    iron, rhodium, ruthenium, palladium, platinum, iridium, osmium,    silver, gold, molybdenum, tungsten, rhenium, cadmium, lead,    manganese, tin, chromium, lithium, sodium, potassium, cesium,    magnesium, barium, phosphorus, arsenic, antimony, bismuth, selenium    and tellurium.

This heterogeneous copper-containing catalyst more preferably comprises,based on the total weight of the catalyst,

-   2-25% by weight of copper;-   3-50% by weight of nickel;-   0-5% by weight of at least one promoter selected from the group of    iron, rhodium, ruthenium, palladium, platinum, iridium, osmium,    silver, gold, molybdenum, tungsten, rhenium, cadmium, lead,    manganese, tin, chromium, lithium, sodium, potassium, cesium,    magnesium, barium, phosphorus, arsenic, antimony, bismuth, selenium    and tellurium, preferably molybdenum.

This copper-containing catalyst preferably comprises, as catalyticallyactive metals, only copper and nickel, especially in each case (butindependently) from 2 to 15% by weight, more preferably from 2 to 10% byweight, especially preferably from 3 to 8% by weight, based on the totalweight of the catalyst. The support material is preferably a porousmetal oxide, especially aluminum oxide, titanium dioxide or zirconiumdioxide.

Equally preferably, this copper-containing catalyst comprises, ascatalytically active metals or promoters, only copper, nickel andmolybdenum, especially from 2 to 25% by weight of copper, from 20 to 60%by weight of nickel, from 0.01 to 5% by weight of molybdenum, morepreferably from 5 to 20% by weight of copper, from 30 to 50% by weightof nickel, from 0.1 to 2% by weight of molybdenum, especially preferablyfrom 10 to 15% by weight of copper, from 35 to 45% by weight of nickel,from 0.5 to 1.5% by weight of molybdenum, based on the total weight ofthe catalyst. The support material is preferably a porous metal oxide,especially aluminum oxide, titanium dioxide or zirconium dioxide.

In a further embodiment, this heterogeneous copper-containing catalystcomprises, based on the total weight of the catalyst,

-   2-40% by weight of copper;-   0.1-80% by weight of at least one metal selected from the group of    nickel and cobalt;-   0-5% by weight of at least one promoter selected from the group of    iron, rhodium, ruthenium, palladium, platinum, iridium, osmium,    silver, gold, molybdenum, tungsten, rhenium, cadmium, lead,    manganese, tin, chromium, lithium, sodium, potassium, cesium,    magnesium, barium, phosphorus, arsenic, antimony, bismuth, selenium    and tellurium.

This heterogeneous copper-containing catalyst preferably comprises,based on the total weight of the catalyst,

-   2-40% by weight of copper;-   0.1-40% by weight of nickel;-   0.1-40% by weight of cobalt;-   0-5% by weight of at least one promoter selected from the group of    iron, rhodium, ruthenium, palladium, platinum, iridium, osmium,    silver, gold, molybdenum, tungsten, rhenium, cadmium, lead,    manganese, tin, chromium, lithium, sodium, potassium, cesium,    magnesium, barium, phosphorus, arsenic, antimony, bismuth, selenium    and tellurium.

This heterogeneous copper-containing catalyst especially comprises,based on the total weight of the catalyst,

-   2-30% by weight of copper;-   0.5-35% by weight of nickel;-   0.5-35% by weight of cobalt;-   0-5% by weight of at least one promoter selected from the group of    iron, rhodium, ruthenium, palladium, platinum, iridium, osmium,    silver, gold, molybdenum, tungsten, rhenium, cadmium, lead,    manganese, tin, chromium, lithium, sodium, potassium, cesium,    magnesium, barium, phosphorus, arsenic, antimony, bismuth, selenium    and tellurium.

This heterogeneous copper-containing catalyst more preferably comprises,based on the total weight of the catalyst,

-   2-20% by weight of copper;-   1-30% by weight of nickel;-   1-30% by weight of cobalt;-   0-5% by weight of at least one promoter selected from the group of    iron, rhodium, ruthenium, palladium, platinum, iridium, osmium,    silver, gold, molybdenum, tungsten, rhenium, cadmium, lead,    manganese, tin, chromium, lithium, sodium, potassium, cesium,    magnesium, barium, phosphorus, arsenic, antimony, bismuth, selenium    and tellurium, preferably molybdenum.

This copper-containing catalyst preferably comprises, as catalyticallyactive metals, only copper, nickel and cobalt, especially from 2 to 25%by weight of copper and in each case independently from 1 to 35% byweight of nickel and/or cobalt, more preferably from 2 to 20% by weightof copper and in each case independently from 10 to 30% by weight ofnickel and/or cobalt, especially preferably from 5 to 15% by weight ofcopper and in each case independently from 15 to 25% by weight of nickeland/or cobalt, based on the total weight of the catalyst. The supportmaterial is preferably a porous metal oxide, especially aluminum oxide,titanium dioxide or zirconium dioxide.

Equally especially, this copper-containing catalyst comprises, ascatalytically active metals, only copper, nickel and cobalt, morepreferably from 2 to 10% by weight of copper and in each caseindependently from 1 to 10% by weight of nickel and/or cobalt,especially preferably from 2 to 5% by weight of copper and in each caseindependently from 2 to 5% by weight of nickel and/or cobalt, based onthe total weight of the catalyst. The support material is preferably aporous metal oxide, especially aluminum oxide, titanium dioxide orzirconium dioxide.

In a further embodiment, this heterogeneous copper-containing catalystcomprises, based on the total weight of the catalyst,

-   2-40% by weight of copper;-   0.1-80% by weight of cobalt;-   0-15% by weight of at least one promoter selected from the group of    iron, rhodium, ruthenium, palladium, platinum, iridium, osmium,    silver, gold, molybdenum, tungsten, rhenium, cadmium, lead,    manganese, tin, chromium, lithium, sodium, potassium, cesium,    magnesium, barium, phosphorus, arsenic, antimony, bismuth, selenium    and tellurium.

In particular, this heterogeneous copper-containing catalyst comprises,based on the total weight of the catalyst,

-   2-20% by weight of copper;-   2-20% by weight of cobalt;-   0-5% by weight of at least one promoter selected from the group of    iron, rhodium, ruthenium, palladium, platinum, iridium, osmium,    silver, gold, molybdenum, tungsten, rhenium, cadmium, lead,    manganese, tin, chromium, lithium, sodium, potassium, cesium,    magnesium, barium, phosphorus, arsenic, antimony, bismuth, selenium    and tellurium.

This heterogeneous copper-containing catalyst more preferably comprises,based on the total weight of the catalyst,

-   2-15% by weight of copper;-   2-15% by weight of cobalt;-   0-5% by weight of at least one promoter selected from the group of    iron, rhodium, ruthenium, palladium, platinum, iridium, osmium,    silver, gold, molybdenum, tungsten, rhenium, cadmium, lead,    manganese, tin, chromium, lithium, sodium, potassium, cesium,    magnesium, barium, phosphorus, arsenic, antimony, bismuth, selenium    and tellurium.

This copper-containing catalyst preferably comprises, as catalyticallyactive metals, only copper and cobalt, especially in each case (butindependently) from 2 to 15% by weight, more preferably from 3 to 10% byweight, especially preferably from 3 to 8% by weight, based on the totalweight of the catalyst. The support material is preferably a porousmetal oxide, especially aluminum oxide, titanium dioxide or zirconiumdioxide.

In a further embodiment, this heterogeneous copper-containing catalystcomprises, based on the total weight of the catalyst,

-   5-40% by weight of copper;-   20-80% by weight of cobalt;-   0-15% by weight of at least one promoter selected from the group of    iron, rhodium, ruthenium, palladium, platinum, iridium, osmium,    silver, gold, molybdenum, tungsten, rhenium, cadmium, lead,    manganese, tin, chromium, lithium, sodium, potassium, cesium,    magnesium, barium, phosphorus, arsenic, antimony, bismuth, selenium    and tellurium.

This heterogeneous copper-containing catalyst more preferably comprises,based on the total weight of the catalyst,

-   10-25% by weight of copper;-   40-70% by weight of cobalt;-   0.1-15% by weight of at least one promoter selected from the group    of iron, rhodium, ruthenium, palladium, platinum, iridium, osmium,    silver, gold, molybdenum, tungsten, rhenium, cadmium, lead,    manganese, tin, chromium, lithium, sodium, potassium, cesium,    magnesium, barium, phosphorus, arsenic, antimony, bismuth, selenium    and tellurium, preferably molybdenum, manganese and phosphorus.

This copper-containing catalyst preferably comprises, as catalyticallyactive metals or promoters, only copper, cobalt, molybdenum andmanganese, especially from 5 to 40% by weight of copper, from 30 to 80%by weight of cobalt and in each case independently from 0.1 to 15% byweight of molybdenum, manganese and phosphorus, more preferably from 10to 35% by weight of copper, from 40 to 75% by weight of cobalt and ineach case independently from 0.5 to 15% by weight of molybdenum,manganese and phosphorus, especially preferably from 12 to 25% by weightof copper, from 45 to 60% by weight of cobalt and in each caseindependently from 0.5 to 15% by weight of molybdenum, manganese andphosphorus, based on the total weight of the catalyst. In a particularembodiment, this catalyst is an unsupported catalyst.

The catalyst typically has a BET surface area (determined to DIN 66131)of from 50 up to 150 m²/g, preferably from 70 to 130 m²/g, especiallyfrom 75 to 120 m²/g. In general, the pore volume of the catalyst(determined by means of Hg porosimetry to DIN 66133) is from 0.1 to 0.4ml/g, preferably from 0.15 to 0.35 ml/g, especially from 0.15 to 0.3ml/g.

The catalyst can, however, also be prepared by customary processes (A.Farkas, in Ullmann's Encyclopedia of Industrial Chemistry, ElectronicRelease 2000, chapters 5.3, 5.4, 5.6 to 5.10).

For example, it is possible to prepare the support from correspondingcompounds which are converted to the oxide of the particular support oncalcination. For this purpose, especially hydroxides, carbonates andcarboxylates are suitable. The oxide or the corresponding precursorwhich is converted to the oxide of the particular support on calcinationcan be prepared by processes known per se, for example by the sol-gelprocess, by precipitation, dewatering of the corresponding carboxylates,dry mixing, slurrying or spray drying. In precipitation, typicallysoluble salts of aluminum, titanium, zirconium etc. are used, forexample the corresponding halides, preferably chloride, alkoxides,nitrate etc., preferably nitrates of aluminum, titanium, zirconium etc.In addition, it is possible to incorporate stabilizers into the supportby customary methods.

It is likewise possible to incorporate assistants into the support,which facilitate the shaping of the support, for example graphite orstearic acid. This is followed by the shaping. In general, extrudates,tablets, spheres, spall, monoliths etc., are prepared by the customarymethods.

The calcination is effected typically with air or a mixture of air andnitrogen, at a temperature of from 300 to 800° C., preferably at from500 to 600° C. It may be advantageous to add water vapor to the air orto the air/nitrogen mixture.

It is now possible to apply the inventive catalytically active metalsand/or promoters to the support. Typically, the support is impregnatedwith a solution of a corresponding metal precursor or promoter precursoror saturated therein. The impregnation can be effected by the incipientwetness method, wherein the porous volume of the support is filled up byabout the same volume of impregnation solution and—if appropriate aftermaturation—the support is dried; or an excess of solution is employed,in which case the volume of this solution is greater than the porousvolume of the support. In this case, the support is mixed with theimpregnation solution and stirred for a sufficiently long period. Theexcess impregnation solution is shaken off, centrifuged off or removedby filtration. From case to case, the addition of acids, neutral saltsor bases may also facilitate the impregnation/saturation. Thoroughimpregnation of the support can be achieved from case to case by, forexample, heating the solution during the impregnation/saturation, addingsurface-active substances or evacuating the support. In addition, it ispossible to spray the support with a solution of the appropriateprecursor. In this case, the appropriate support is treated with asolution of the appropriate metal precursor and/or promoter precursor,which is such that the support absorbs the solution.

However, other preparation methods known to those skilled in the art,for example chemical vapor deposition, sol impregnation etc., are alsopossible.

Suitable metal precursors and/or promoter precursors are correspondingsoluble metal salts, including halides, especially chloride, nitrate,acetate, alkaline carbonates, formate, oxalate, citrate, tartrate.

The metal and/or promoter precursors can be applied together orsuccessively by the aforementioned methods. It may also be advantageousto comply with a certain sequence here.

However, other preparation methods known to those skilled in the art,for example chemical vapor deposition, sol impregnation etc., are alsopossible.

The support to which the inventive catalytically active metal precursorsare applied is now calcined. The calcination is effected typically withair or a mixture of air and nitrogen, at a temperature of from 300 to800° C., preferably at from 400 to 600° C. It may be advantageous to addwater vapor to the air or to the air/nitrogen mixture.

After the calcination, the heterogeneous copper-containing catalyst isappropriately conditioned, whether by adjusting it to a particularparticle size by grinding or by mixing it with shaping assistants suchas graphite or stearic acid after it has been ground, pressed topressings by means of a tableting press and heat-treated. The heattreatment temperatures correspond generally to the temperatures in thecalcination.

However, it is also possible to prepare the heterogeneouscopper-containing catalysts by employing precipitation methods. Forexample, they can be obtained by a coprecipitation of the metal and/orpromoter precursors from an aqueous salt solution comprising thesemetals/promoters by means of mineral bases in the presence of a slurryof a sparingly soluble, oxygen-containing support precursor compound orof the support itself, and subsequent washing, drying and calcination ofthe resulting precipitate.

The sparingly soluble, oxygen-containing support precursor compounds orsupports themselves used may, for example, be oxides, oxyhydrates,phosphates, borates and silicates, for example oxides, oxyhydrates,phosphates, borates and silicates, for example zirconium dioxide,zirconium oxide hydrate, zirconium phosphates, borates and silicates,silicon dioxide, aluminum oxide, aluminum oxyhydrate, titanium dioxide,and further compounds which are suitable for this purpose and are knownto those skilled in the art. The slurries of the sparingly solublesupport precursor compounds or supports themselves can be prepared bysuspending fine powders of these support precursor compounds or supportsthemselves in water with vigorous stirring. Advantageously, theseslurries are prepared by precipitating the sparingly soluble supportprecursor compounds from aqueous salt solutions by means of mineralbases.

In particular, the inventive heterogeneous copper-containing catalystsare prepared by means of a coprecipitation of all of their components.To this end, an aqueous salt solution comprising the catalystcomponents, under hot conditions and with stirring, is admixed with anaqueous mineral base, especially an alkali metal base—for example sodiumcarbonate, sodium hydroxide, potassium carbonate or potassiumhydroxide—until the precipitation is complete. The type of salts used isgenerally not critical—since the principal factor in this procedure isthe water solubility of the salts, a criterion is their good watersolubility, which is required to prepare these comparatively highlyconcentrated salt solutions. It is considered to be obvious that, whenselecting the salts of the individual components, of course, only saltswith those anions which do not lead to disruption, whether by causingundesired precipitation or by complicating or preventing precipitationby complex formation, are selected.

The precipitates obtained in these precipitation reactions are generallychemically inhomogeneous and consist, inter alia, of mixtures of theoxides, oxide hydrates, hydroxides, carbonates and insoluble and basicsalts of the metals/promoters used. It may be found to be favorable forthe filterability of the precipitates if they are aged, i.e. if they areleft alone for a certain time after precipitation, if appropriate underhot conditions or while passing air through.

The precipitates obtained by these precipitation reactions are processedfurther as usual to give the inventive heterogeneous copper-containingcatalysts. After washing, they are generally dried at from 80 to 200°C., preferably at from 100 to 150° C., and then calcined. Thecalcination (heat treatment) is generally performed at temperaturesbetween 300 and 800° C., preferably at from 400 to 600° C., especiallyat from 450 to 550° C.

After the calcination, the heterogeneous copper-containing catalyst isappropriately conditioned, whether by adjusting it to a particularparticle size by grinding or by mixing it with shaping assistants suchas graphite or stearic acid after it has been ground, pressed topressings by means of a tableting press and heat-treated. The heattreatment temperatures correspond generally to the temperatures in thecalcination.

The heterogeneous copper-containing catalysts obtained in this waycomprise the catalytically active metals/promoters in the form of amixture of their oxygen compounds, i.e. especially as the oxides andmixed oxides. The heterogeneous copper-containing catalysts obtained inthis way can be stored as such.

The catalyst thus obtained can be activated before use in thediaselective hydrogenation of compounds of the formula I. To this end,it is treated with hydrogen or a mixture of hydrogen and nitrogen attemperatures of from 100 to 300° C. In this case, it may be advantageousto begin with a low hydrogen fraction in the hydrogen/nitrogen mixtureand to increase the hydrogen fraction continuously or in stages in thecourse of the activation process. The prereduction can be carried out,for example, first at from 150 to 200° C. over a period of from 12 to 20hours in a nitrogen/hydrogen atmosphere, and then continued for anotherapprox. 24 hours at from 200 to 300° C. in a hydrogen atmosphere.

The activation of the catalyst is generally carried out in the reactorin which the inventive hydrogenation is to be effected. However, it isalso possible to undertake the activation of the catalyst beforeinstallation into the reactor in question.

Typically, the catalyst is used in reduced form in the inventivehydrogenation. In this context, it may be advantageous to activate thecatalyst present in reduced form once again. To this end, it is treatedwith hydrogen or a mixture of hydrogen and an inert gas, e.g. nitrogen,at temperatures of from room temperature to 300° C., preferably at from150 to 300° C., and a hydrogen pressure of from 10 to 60 bar, preferablyat max. 50 bar. In this context, it may be advantageous to activate withhydrogen without inert gas. However, it may also be advantageous toactivate with a mixture of hydrogen and inert gas, in which case tobegin with the hydrogen/inert gas mixture and to increase the hydrogenfraction continuously in the course of the activation process.

However, it is also possible to use the catalyst, in its oxidic form orelse in its reduced form, in the diaselective hydrogenation of imines ofthe formula I without any further prior activation.

The process according to the invention can be performed batchwise,semicontinuously or continuously.

In a batchwise procedure, the reaction mixture is worked up by customarymethods, for example by removing the catalyst, for example byfiltration, allowing it to settle and removing the liquid phase or bycentrifugation, and the solvent is removed from the filtrate,supernatant or centrifugate thus obtained, for example, by distilling itoff. The inventive hydrogenation is carried out in the hydrogenationreactors known to those skilled in the art. Examples thereof includeso-called slurry reactors, trickle-bed reactors and bubble columns (P.N. Rylander, Ullmann's Encyclopedia, Electronic Release 2007, chapter:Hydrogenation and Dehydrogenation, p. 2-3).

In general, the hydrogenation of the imines of the formula I willproceed in the liquid phase, for example in a stirred autoclave, abubble column, a circulation reactor, for instance a loop reactor or afixed bed reactor. The fixed bed reactor can be operated either inliquid phase mode or in trickle mode.

However, it is also possible, especially when the imine of the formula Iexhibits a certain degree of volatility, to perform the hydrogenationwithout solvent in the gas phase. Examples of suitable reactors for thispurpose are fixed bed reactors or fluidized bed reactors.

The reaction output can be worked up and purified by the customarymethods. Examples of useful methods for this purpose are distillation,liquid extraction and/or crystallization.

The compounds of the formula II obtained by the process according to theinvention have a diastereomeric ratio of >0.70, preferably >0.9,especially >0.95, exceptionally preferably of >0.98 (where thediastereomeric ratio is the molar ratio of desired diastereomer:undesired diastereomer). If it is desirable to achieve an even higherdiastereomeric ratio, the diastereomeric ratio of the compounds of theformula II obtained by the process according to the invention can beincreased by known methods, for example recrystallization.

The diastereomeric ratio can be determined by customary methods known tothose skilled in the art; typically, it is determined indirectly via therotation or directly by means of gas or liquid chromatography. Thedetermination can be effected directly or via appropriate derivatives ofthe target compound.

The catalyst can be reused in the process according to the invention.

The compounds of the formula I are known or can be prepared byliterature methods.

For example, it is possible to obtain the compounds of the formula I byreacting ketones of the formula III with amines of the formula IV, wherethe R¹ to R⁴ radicals are each as defined for the compounds of theformula I.

Typically, the ketone of the formula III and the amine of the formula IVare used in stoichiometric amounts. From case to case, it may also beadvantageous to use one or the other reactant in excess. In general, thereaction is carried out in a solvent. Suitable solvents are inertsolvents, for example alcohols, ethers, hydrocarbons, halogenatedhydrocarbons etc., especially those which form an azeotrope with water,for example toluene or ethylbenzene, thus allowing the water formed inthe reaction to be removed. When one of the reactants used forms anazeotropic mixture with water, this reactant can be used in excess, andthe water formed can be removed azeotropically. This can be done in thepresence or in the absence of an additional solvent. In addition, it maybe advantageous from case to case to add catalytic amounts of acid, forexample p-toluenesulfonic acid. The reaction can also be carried out inthe presence of heterogeneous catalysts, for example aluminum oxides,titanium dioxide, zirconium dioxide, silicon oxides, or clay mineralssuch as montmorillonite.

From case to case, it may also be advantageous to scavenge the waterreleased in the reaction with a molecular sieve. Alternatively, it mayalso be advantageous to distill off the water formed in the reaction.The reaction takes place typically at a temperature from roomtemperature to reflux temperature of the reaction mixture. The reactionmixture is worked up by the methods known to those skilled in the art.

In the abovementioned reaction, instead of the chiral amine of theformula IV, it is also possible to use a corresponding racemate. Oncompletion of reaction and if appropriate workup, a racemate separationcan be carried out by the methods known to those skilled in the art.

The compounds of the formula I can also be obtained by reacting analkyne of the formula V with an amine of the formula IV.

The definitions of the R² to R⁴ radicals correspond to those specifiedfor the compounds of the formula I. And R^(1′)—CH₂ represents thedefinitions of R¹ which are compatible therewith. The same applies toR^(1′).

Typically, the alkyne of the formula V and the amine of the formula IVare used in a stoichiometric ratio. However, it may be advantageous touse the alkyne of the formula V in excess. The reaction is generallycarried out in an inert solvent, for example an ether, a hydrocarbon, ahalogenated hydrocarbon etc., or mixtures thereof, at from roomtemperature to reflux temperature of the reaction mixture. In general,the reaction is carried out at standard pressure. From case to case,however, it may also be advantageous to carry out the reaction atelevated pressure, preferably in the range from 10 to 200 bar.Completion of reaction is followed by workup by the methods known tothose skilled in the art.

In the abovementioned reaction, instead of the chiral amine of theformula IV, it is also possible to use a corresponding racemate. Oncompletion of reaction and if appropriate workup, a racemate separationcan be carried out by the methods known to those skilled in the art.

It is equally possible to prepare the imines of the formula I byreacting nitroso compounds of the formula VII with phosphorus ylides ofthe formula VI.

The R¹ to R⁴ radicals are each as defined under the compounds of theformula I.

Typically, the phosphorus ylide of the formula VI and the nitrosocompound of the formula VII are used in a stoichiometric ratio. Fromcase to case, however, it may also be advantageous to use one or theother reaction component in excess or in deficiency. The reaction isgenerally carried out in an inert solvent, for example an ether, ahydrocarbon, a halogenated hydrocarbon etc., or mixtures thereof, atfrom room temperature to reflux temperature of the reaction mixture. Ingeneral, the reaction is carried out at standard pressure. Completion ofreaction is followed by workup by the methods known to those skilled inthe art.

In the abovementioned reaction, instead of the chiral nitroso compoundof the formula VII, it is also possible to use a corresponding racemate.On completion of reaction and if appropriate workup, a racemateseparation can be carried out by the methods known to those skilled inthe art.

The preparation of the imines of the formula I can be carried outcontinuously, semicontinuously or batchwise.

Preference is given to using, in the process according to the invention,imines of the formula I, or amines of the formula II, where the radicalsare each independently defined as follows:

-   R¹, R² are each C₁-C₆-alkyl, C₃-C₆-cycloalkyl, C₂-C₆-alkenyl,    C₂-C₆-alkynyl, C₂-C₆-haloalkenyl, C₂-C₆-haloalkynyl or    C₁-C₆-alkylcarbonyl-C₁-C₆-alkyl, where the alkyl, cycloalkyl and    alkoxy radicals mentioned may be partially or fully halogenated    and/or may bear from one to three of the following groups: cyano,    hydroxyl, C₁-C₄-alkyl, C₃-C₆-cycloalkyl, C₁-C₆-alkoxy-C₁-C₄-alkyl,    C₁-C₄-alkoxy-C₁-C₄-alkoxy-C₁-C₄-alkyl, C₁-C₄-alkoxy,    C₁-C₄-alkylthio, amino, C₁-C₄-alkylamino, di(C₁-C₄-alkyl)amino;    -   aryl, aryl-C₁-C₄-alkyl, aryl-C₂-C₄-alkenyl, aryl-C₂-C₄-alkynyl,        aryl-C₁-C₄-haloalkyl, aryl-C₂-C₄-haloalkenyl,        aryl-C₃-C₄-haloalkynyl, aryl-C₁-C₄-hydroxyalkyl,        arylcarbonyl-C₁-C₄-alkyl, aryl-C₁-C₄-alkylcarbonyl-C₁-C₄-alkyl,        aryloxy-C₁-C₄-alkyl, arylamino-C₁-C₄-alkyl,        arylthio-C₁-C₄-alkyl, arylsulfinyl-C₁-C₄-alkyl,        arylsulfonyl-C₁-C₄-alkyl, heterocyclyl,        heterocyclyl-C₁-C₄-alkyl, heterocyclyl-C₂-C₄-alkenyl,        heterocyclyl-C₂-C₄-alkynyl, heterocyclyl-C₁-C₄-haloalkyl,        heterocyclyl-C₂-C₄-haloalkenyl, heterocyclyl-C₃-C₄-haloalkynyl,        heterocyclyl-C₁-C₄-hydroxyalkyl,        heterocyclylcarbonyl-C₁-C₄-alkyl,        heterocyclyl-C₁-C₄-alkylcarbonyl-C₁-C₄-alkyl,        heterocyclyloxy-C₁-C₄-alkyl, heterocyclylamino-C₁-C₄-alkyl,        heterocyclylthio-C₁-C₄-alkyl, heterocyclylsulfinyl-C₁-C₄-alkyl,        heterocyclylsulfonyl-C₁-C₄-alkyl, where the aforementioned        radicals may be partially or fully halogenated and/or may bear        from one to three radicals from the group of cyano, nitro,        C₁-C₆-alkyl, C₁-C₆-haloalkyl, hydroxyl, C₁-C₆-hydroxyalkyl,        C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, C₁-C₆-alkoxycarbonyl,        di(C₁-C₆-alkyl)aminocarbonyl, amino, C₁-C₆-alkylamino,        di(C₁-C₆-alkyl)amino, C₁-C₆-alkylsulfonylamino,        C₁-C₆-haloalkylsulfonylamino, aryl and aryl(C₁-C₆-alkyl);-   R³ is C₁-C₄-alkyl, preferably methyl; and-   R⁴ is aryl which may be partially or fully halogenated and/or may    bear from one to three radicals from the group of cyano, nitro,    C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, aryl    and aryl(C₁-C₆-alkyl); preferably phenyl or 1-naphthyl;

In particular, in the process according to the invention, imines of theformula I are used, or amines of the formula II are prepared, where theradicals are each independently defined as follows:

-   R¹, R² are each C₁-C₆-alkyl or C₃-C₆-cycloalkyl, where the alkyl or    cycloalkyl radicals mentioned may be partially or fully halogenated    and/or may bear from one to three of the following groups: cyano,    hydroxyl, C₃-C₆-cycloalkyl, C₁-C₆-alkoxy-C₁-C₄-alkyl,    C₁-C₄-alkoxy-C₁-C₄-alkoxy-C₁-C₄-alkyl, C₁-C₄-alkoxy,    C₁-C₄-alkylthio, amino, C₁-C₄-alkylamino, di(C₁-C₄-alkyl)amino,    C₁-C₄-alkylcarbonylamino, hydroxycarbonyl, C₁-C₄-alkoxycarbonyl,    aminocarbonyl, C₁-C₄-alkylaminocarbonyl,    di(C₁-C₄-alkyl)aminocarbonyl or C₁-C₄-alkylcarbonyloxy; especially    C₁-C₆-alkyl or C₃-C₆-cycloalkyl, where the alkyl or cycloalkyl    radicals mentioned may be partially or fully halogenated and/or may    bear one of the following groups: cyano, C₁-C₄-alkoxy,    C₁-C₄-alkylthio, di(C₁-C₄-alkyl)amino, C₁-C₄-alkoxycarbonyl,    di(C₁-C₄-alkyl)aminocarbonyl or C₁-C₄-alkylcarbonyloxy; likewise    especially C₁-C₆-alkyl or C₃-C₆-cycloalkyl, where the alkyl or    cycloalkyl radicals mentioned may be partially or fully halogenated    and/or may bear from one to three of the following groups: cyano,    C₁-C₄-alkoxycarbonyl, di(C₁-C₄-alkyl)aminocarbonyl or    C₁-C₄-alkylcarbonyloxy;    -   more preferably C₁-C₆-alkyl, where the alkyl radical mentioned        may be partially or fully halogenated and/or may bear from one        to three of the following groups: cyano, di(C₁-C₄-alkyl)amino,        C₁-C₄-alkoxycarbonyl, di(C₁-C₄-alkyl)aminocarbonyl or        C₁-C₄-alkylcarbonyloxy;    -   exceptionally preferably C₁-C₆-alkyl;    -   phenyl, phenyl-C₁-C₄-alkyl, phenyl-C₂-C₄-alkenyl,        phenyl-C₂-C₄-alkynyl, phenyl-C₁-C₄-haloalkyl,        phenyl-C₂-C₄-haloalkenyl, phenyl-C₃-C₄-haloalkynyl,        phenyl-C₁-C₄-hydroxyalkyl, phenylcarbonyl-C₁-C₄-alkyl,        phenyl-C₁-C₄-alkylcarbonyl-C₁-C₄-alkyl,        phenylcarbonyloxy-C₁-C₄-alkyl, phenyloxycarbonyl-C₁-C₄-alkyl,        phenyloxy-C₁-C₄-alkyl, phenylamino-C₁-C₄-alkyl,        phenylthio-C₁-C₄-alkyl, phenylsulfinyl-C₁-C₄-alkyl,        phenylsulfonyl-C₁-C₄-alkyl,    -   heterocyclyl, heterocyclyl-C₁-C₄-alkyl,        heterocyclyl-C₂-C₄-alkenyl, heterocyclyl-C₂-C₄-alkynyl,        heterocyclyl-C₁-C₄-haloalkyl, heterocyclyl-C₂-C₄-haloalkenyl,        heterocyclyl-C₃-C₄-haloalkynyl, heterocyclyl-C₁-C₄-hydroxyalkyl,        heterocyclylcarbonyl-C₁-C₄-alkyl,        heterocyclyl-C₁-C₄-alkylcarbonyl-C₁-C₄-alkyl,        heterocyclylcarbonyloxy-C₁-C₄-alkyl,        heterocyclyloxycarbonyl-C₁-C₄-alkyl,        heterocyclyloxy-C₁-C₄-alkyl, heterocyclylamino-C₁-C₄-alkyl,        heterocyclylthio-C₁-C₄-alkyl, heterocyclylsulfinyl-C₁-C₄-alkyl,        heterocyclylsulfonyl-C₁-C₄-alkyl, where the aforementioned        radicals may be partially or fully halogenated and/or may bear        from one to three radicals from the group of cyano, nitro,        C₁-C₆-alkyl, C₁-C₆-haloalkyl, hydroxyl, C₁-C₆-hydroxyalkyl,        C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, hydroxycarbonyl,        C₁-C₆-alkoxycarbonyl, aminocarbonyl,        (C₁-C₆-alkyl)amino-carbonyl, di(C₁-C₆-alkyl)aminocarbonyl,        hydroxycarbonyl-C₁-C₆-alkoxy, C₁-C₆-alkoxycarbonyl-C₁-C₆-alkoxy,        amino, C₁-C₆-alkylamino, di(C₁-C₆-alkyl)amino,        C₁-C₆-alkylsulfonylamino, C₁-C₆-haloalkylsulfonylamino,        (C₁-C₆-alkyl)amino-carbonylamino,        di(C₁-C₆-alkyl)aminocarbonylamino, aryl and aryl(C₁-C₆-alkyl);        especially phenyl, phenyl-C₁-C₄-alkyl, phenyl-C₂-C₄-alkenyl,        phenyl-C₁-C₄-haloalkyl, phenyl-C₁-C₄-hydroxyalkyl,        phenylcarbonyl-C₁-C₄-alkyl,        phenyl-C₁-C₄-alkylcarbonyl-C₁-C₄-alkyl,        phenylcarbonyloxy-C₁-C₄-alkyl, phenyloxycarbonyl-C₁-C₄-alkyl,        phenyloxy-C₁-C₄-alkyl, phenylamino-C₁-C₄-alkyl,        phenylthio-C₁-C₄-alkyl, phenylsulfonyl-C₁-C₄-alkyl,    -   heterocyclyl, heterocyclyl-C₁-C₄-alkyl,        heterocyclyl-C₂-C₄-alkenyl, heterocyclyl-C₁-C₄-haloalkyl,        heterocyclyl-C₁-C₄-hydroxyalkyl,        heterocyclylcarbonyl-C₁-C₄-alkyl,        heterocyclyl-C₁-C₄-alkylcarbonyl-C₁-C₄-alkyl,        heterocyclylcarbonyloxy-C₁-C₄-alkyl,        heterocyclyloxycarbonyl-C₁-C₄-alkyl,        heterocyclyloxy-C₁-C₄-alkyl, heterocyclylamino-C₁-C₄-alkyl,        heterocyclylthio-C₁-C₄-alkyl, heterocyclylsulfonyl-C₁-C₄-alkyl,    -   where the aforementioned radicals may be partially or fully        halogenated and/or may bear from one to three radicals from the        group of cyano, nitro, C₁-C₆-alkyl, C₁-C₆-haloalkyl, hydroxyl,        C₁-C₆-hydroxyalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy,        hydroxycarbonyl, C₁-C₆-alkoxycarbonyl, aminocarbonyl,        (C₁-C₆-alkyl)amino-carbonyl, di(C₁-C₆-alkyl)aminocarbonyl,        hydroxycarbonyl-C₁-C₆-alkoxy, di(C₁-C₆-alkyl)amino,        di(C₁-C₆-alkyl)aminocarbonylamino, aryl and aryl(C₁-C₆-alkyl);        more preferably phenyl, phenyl-C₁-C₄-alkyl,        phenyl-C₁-C₄-haloalkyl, phenylcarbonyloxy-C₁-C₄-alkyl,        phenyloxycarbonyl-C₁-C₄-alkyl, phenyloxy-C₁-C₄-alkyl,    -   heterocyclyl, heterocyclyl-C₁-C₄-alkyl,        heterocyclyl-C₁-C₄-haloalkyl,        heterocyclylcarbonyloxy-C₁-C₄-alkyl,        heterocyclyloxycarbonyl-C₁-C₄-alkyl,        heterocyclyloxy-C₁-C₄-alkyl,    -   where the aforementioned radicals may be partially or fully        halogenated and/or may bear from one to three radicals from the        group of cyano, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy,        C₁-C₆-haloalkoxy, hydroxycarbonyl, C₁-C₆-alkoxy-carbonyl,        aminocarbonyl, (C₁-C₆-alkyl)aminocarbonyl,        di(C₁-C₆-alkyl)-aminocarbonyl, di(C₁-C₆-alkyl)amino, aryl and        aryl(C₁-C₆-alkyl);-   R³ is C₁-C₄-alkyl, preferably methyl; and-   R⁴ is aryl which may be partially or fully halogenated and/or may    bear from one to three radicals from the group of cyano, nitro,    C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, aryl    and aryl(C₁-C₆-alkyl); preferably phenyl or 1-naphthyl.

Particular preference is given, in the process according to theinvention, to using imines of the formula I, or to preparing amines ofthe formula II, where the radicals are each independently defined asfollows:

-   R¹, R² are each C₁-C₆-alkyl or C₃-C₆-cycloalkyl, where the alkyl or    cycloalkyl radicals mentioned may be partially or fully halogenated    and/or may bear from one to three of the following groups: cyano,    hydroxyl, C₃-C₆-cycloalkyl, C₁-C₆-alkoxy-C₁-C₄-alkyl,    C₁-C₄-alkoxy-C₁-C₄-alkoxy-C₁-C₄-alkyl, C₁-C₄-alkoxy,    C₁-C₄-alkylthio, amino, C₁-C₄-alkylamino, di(C₁-C₄-alkyl)amino,    C₁-C₄-alkyl-carbonylamino, hydroxycarbonyl, C₁-C₄-alkoxycarbonyl,    aminocarbonyl, C₁-C₄-alkylaminocarbonyl,    di(C₁-C₄-alkyl)aminocarbonyl or C₁-C₄-alkylcarbonyloxy; especially    C₁-C₆-alkyl or C₃-C₆-cycloalkyl, where the alkyl or cycloalkyl    radicals mentioned may be partially or fully halogenated and/or may    bear one of the following groups: cyano, C₁-C₄-alkoxy,    C₁-C₄-alkylthio, di(C₁-C₄-alkyl)amino, C₁-C₄-alkoxycarbonyl,    di(C₁-C₄-alkyl)aminocarbonyl or C₁-C₄-alkylcarbonyloxy; likewise    especially C₁-C₆-alkyl or C₃-C₆-cycloalkyl, where the alkyl or    cycloalkyl radicals mentioned may be partially or fully halogenated    and/or may bear from one to three of the following groups: cyano,    C₁-C₄-alkoxycarbonyl, di(C₁-C₄-alkyl)aminocarbonyl or    C₁-C₄-alkylcarbonyloxy;    -   more preferably C₁-C₆-alkyl, where the alkyl radical mentioned        may be partially or fully halogenated and/or may bear from one        to three of the following groups: cyano, di(C₁-C₄-alkyl)amino,        C₁-C₄-alkoxycarbonyl, di(C₁-C₄-alkyl)aminocarbonyl or        C₁-C₄-alkylcarbonyloxy;    -   exceptionally preferably C₁-C₆-alkyl;-   R³ is C₁-C₄-alkyl, preferably methyl; and-   R⁴ is aryl which may be partially or fully halogenated and/or may    bear from one to three radicals from the group of cyano, nitro,    C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, aryl    and aryl(C₁-C₆-alkyl);    -   preferably phenyl or 1-naphthyl which may be partially or fully        halogenated and/or may bear from one to three radicals from the        group of cyano, nitro, C₁-C₆-alkyl, C₁-C₆-haloalkyl,        C₁-C₆-C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, aryl and        aryl(C₁-C₆-alkyl);    -   especially phenyl or 1-naphthyl.

Particular preference is likewise given, in the process according to theinvention, to using imines of the formula I, or to preparing amines ofthe formula II, where the radicals are each independently defined asfollows:

-   R¹ is C₁-C₆-alkyl or C₃-C₆-cycloalkyl, where the alkyl or cycloalkyl    radicals mentioned may be partially or fully halogenated and/or may    bear from one to three of the following groups: cyano, hydroxyl,    C₃-C₆-cycloalkyl, C₁-C₆-alkoxy-C₁-C₄-alkyl,    C₁-C₄-alkoxy-C₁-C₄-alkoxy-C₁-C₄-alkyl, C₁-C₄-alkoxy,    C₁-C₄-alkylthio, amino, C₁-C₄-alkylamino, di(C₁-C₄-alkyl)amino,    C₁-C₄-alkylcarbonylamino, hydroxycarbonyl, C₁-C₄-alkoxycarbonyl,    aminocarbonyl, C₁-C₄-alkyl-aminocarbonyl,    di(C₁-C₄-alkyl)aminocarbonyl or C₁-C₄-alkylcarbonyloxy; especially    C₁-C₆-alkyl or C₃-C₆-cycloalkyl, where the alkyl or cycloalkyl    radicals mentioned may be partially or fully halogenated and/or may    bear one of the following groups: cyano, C₁-C₄-alkoxy,    C₁-C₄-alkylthio, di(C₁-C₄-alkyl)amino, C₁-C₄-alkoxycarbonyl,    di(C₁-C₄-alkyl)aminocarbonyl or C₁-C₄-alkylcarbonyloxy; likewise    especially C₁-C₆-alkyl or C₃-C₆-cycloalkyl, where the alkyl or    cycloalkyl radicals mentioned may be partially or fully halogenated    and/or may bear from one to three of the following groups: cyano,    C₁-C₄-alkoxycarbonyl, di(C₁-C₄-alkyl)aminocarbonyl or    C₁-C₄-alkylcarbonyloxy;    -   more preferably C₁-C₆-alkyl, where the alkyl radical mentioned        may be partially or fully halogenated and/or may bear from one        to three of the following groups: cyano, di(C₁-C₄-alkyl)amino,        C₁-C₄-alkoxycarbonyl, di(C₁-C₄-alkyl)aminocarbonyl or        C₁-C₄-alkylcarbonyloxy;    -   exceptionally preferably C₁-C₆-alkyl;-   R² is aryl, aryl-C₁-C₄-alkyl, aryl-C₂-C₄-alkenyl,    aryl-C₂-C₄-alkynyl, aryl-C₁-C₄-haloalkyl, aryl-C₂-C₄-haloalkenyl,    aryl-C₃-C₄-haloalkynyl, aryl-C₁-C₄-hydroxyalkyl,    arylcarbonyl-C₁-C₄-alkyl, aryl-C₁-C₄-alkylcarbonyl-C₁-C₄-alkyl,    arylcarbonyloxy-C₁-C₄-alkyl, aryloxycarbonyl-C₁-C₄-alkyl,    aryloxy-C₁-C₄-alkyl, arylamino-C₁-C₄-alkyl, arylthio-C₁-C₄-alkyl,    arylsulfinyl-C₁-C₄-alkyl, arylsulfonyl-C₁-C₄-alkyl, heterocyclyl,    heterocyclyl-C₁-C₄-alkyl, heterocyclyl-C₂-C₄-alkenyl,    heterocyclyl-C₂-C₄-alkynyl, heterocyclyl-C₁-C₄-haloalkyl,    heterocyclyl-C₂-C₄-haloalkenyl, heterocyclyl-C₃-C₄-haloalkynyl,    heterocyclyl-C₁-C₄-hydroxyalkyl, heterocyclyl carbonyl-C₁-C₄-alkyl,    heterocyclyl-C₁-C₄-alkylcarbonyl-C₁-C₄-alkyl,    heterocyclylcarbonyloxy-C₁-C₄-alkyl,    heterocyclyloxycarbonyl-C₁-C₄-alkyl, heterocyclyloxy-C₁-C₄-alkyl,    heterocyclylamino-C₁-C₄-alkyl, heterocyclylthio-C₁-C₄-alkyl,    heterocyclylsulfinyl-C₁-C₄-alkyl, heterocyclylsulfonyl-C₁-C₄-alkyl,    where the aforementioned radicals may be partially or fully    halogenated and/or may bear from one to three radicals from the    group of cyano, nitro, C₁-C₆-alkyl, C₁-C₆-haloalkyl, hydroxyl,    C₁-C₆-hydroxyalkyl, hydroxycarbonyl-C₁-C₆-alkyl,    C₁-C₆-alkoxycarbonyl-C₁-C₆-alkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy,    hydroxycarbonyl, C₁-C₆-alkoxycarbonyl, aminocarbonyl,    (C₁-C₆-alkyl)aminocarbonyl, di(C₁-C₆-alkyl)aminocarbonyl,    hydroxycarbonyl-C₁-C₆-alkoxy, C₁-C₆-alkoxycarbonyl-C₁-C₆-alkoxy,    amino, C₁-C₆-alkylamino, di(C₁-C₆-alkyl)amino,    C₁-C₆-alkylsulfonylamino, C₁-C₆-haloalkylsulfonylamino,    (C₁-C₆-alkyl)aminocarbonylamino, di(C₁-C₆-alkyl)-aminocarbonylamino,    aryl and aryl(C₁-C₆-alkyl);    -   preferably phenyl, phenyl-C₁-C₄-alkyl, phenyl-C₂-C₄-alkenyl,        phenyl-C₂-C₄-alkynyl, phenyl-C₁-C₄-haloalkyl,        phenyl-C₂-C₄-haloalkenyl, phenyl-C₃-C₄-haloalkynyl,        phenyl-C₁-C₄-hydroxyalkyl, phenylcarbonyl-C₁-C₄-alkyl,        phenyl-C₁-C₄-alkylcarbonyl-C₁-C₄-alkyl,        phenylcarbonyloxy-C₁-C₄-alkyl, phenyloxycarbonyl-C₁-C₄-alkyl,        phenyloxy-C₁-C₄-alkyl, phenylamino-C₁-C₄-alkyl,        phenylthio-C₁-C₄-alkyl, phenylsulfinyl-C₁-C₄-alkyl,        phenylsulfonyl-C₁-C₄-alkyl,    -   heterocyclyl, heterocyclyl-C₁-C₄-alkyl,        heterocyclyl-C₂-C₄-alkenyl, heterocyclyl-C₂-C₄-alkynyl,        heterocyclyl-C₁-C₄-haloalkyl, heterocyclyl-C₂-C₄-haloalkenyl,        heterocyclyl-C₃-C₄-haloalkynyl, heterocyclyl-C₁-C₄-hydroxyalkyl,        heterocyclyl-carbonyl-C₁-C₄-alkyl,        heterocyclyl-C₁-C₄-alkylcarbonyl-C₁-C₄-alkyl,        heterocyclylcarbonyloxy-C₁-C₄-alkyl,        heterocyclyloxycarbonyl-C₁-C₄-alkyl,        heterocyclyloxy-C₁-C₄-alkyl, heterocyclylamino-C₁-C₄-alkyl,        heterocyclylthio-C₁-C₄-alkyl, heterocyclylsulfinyl-C₁-C₄-alkyl,        heterocyclylsulfonyl-C₁-C₄-alkyl, where the aforementioned        radicals may be partially or fully halogenated and/or may bear        from one to three radicals from the group of cyano, nitro,        C₁-C₆-alkyl, C₁-C₆-haloalkyl, hydroxyl, C₁-C₆-hydroxyalkyl,        C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, hydroxycarbonyl,        C₁-C₆-alkoxycarbonyl, aminocarbonyl,        (C₁-C₆-alkyl)amino-carbonyl, di(C₁-C₆-alkyl)aminocarbonyl,        hydroxycarbonyl-C₁-C₆-alkoxy, C₁-C₆-alkoxycarbonyl-C₁-C₆-alkoxy,        amino, C₁-C₆-alkylamino, di(C₁-C₆-alkyl)amino,        C₁-C₆-alkylsulfonylamino, C₁-C₆-haloalkylsulfonylamino,        (C₁-C₆-alkyl)amino-carbonylamino,        di(C₁-C₆-alkyl)aminocarbonylamino, aryl and aryl(C₁-C₆-alkyl);    -   especially phenyl, phenyl-C₁-C₄-alkyl, phenyl-C₂-C₄-alkenyl,        phenyl-C₁-C₄-haloalkyl, phenyl-C₁-C₄-hydroxyalkyl,        phenylcarbonyl-C₁-C₄-alkyl,        phenyl-C₁-C₄-alkylcarbonyl-C₁-C₄-alkyl,        phenylcarbonyloxy-C₁-C₄-alkyl, phenyloxycarbonyl-C₁-C₄-alkyl,        phenyloxy-C₁-C₄-alkyl, phenylamino-C₁-C₄-alkyl,        phenylthio-C₁-C₄-alkyl, phenylsulfonyl-C₁-C₄-alkyl,    -   heterocyclyl, heterocyclyl-C₁-C₄-alkyl,        heterocyclyl-C₂-C₄-alkenyl, heterocyclyl-C₁-C₄-haloalkyl,        heterocyclyl-C₁-C₄-hydroxyalkyl,        heterocyclylcarbonyl-C₁-C₄-alkyl,        heterocyclyl-C₁-C₄-alkylcarbonyl-C₁-C₄-alkyl,        heterocyclylcarbonyloxy-C₁-C₄-alkyl,        heterocyclyloxycarbonyl-C₁-C₄-alkyl,        heterocyclyloxy-C₁-C₄-alkyl, heterocyclylamino-C₁-C₄-alkyl,        heterocyclylthio-C₁-C₄-alkyl, heterocyclylsulfonyl-C₁-C₄-alkyl,    -   where the aforementioned radicals may be partially or fully        halogenated and/or may bear from one to three radicals from the        group of cyano, nitro, C₁-C₆-alkyl, C₁-C₆-haloalkyl, hydroxyl,        C₁-C₆-hydroxyalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy,        hydroxycarbonyl, C₁-C₆-alkoxycarbonyl, aminocarbonyl,        (C₁-C₆-alkyl)amino-carbonyl, di(C₁-C₆-alkyl)aminocarbonyl,        hydroxycarbonyl-C₁-C₆-alkoxy, di(C₁-C₆-alkyl)amino,        di(C₁-C₆-alkyl)aminocarbonylamino, aryl and aryl(C₁-C₆-alkyl);    -   more preferably phenyl, phenyl-C₁-C₄-alkyl,        phenyl-C₁-C₄-haloalkyl, phenylcarbonyloxy-C₁-C₄-alkyl,        phenyloxycarbonyl-C₁-C₄-alkyl, phenyloxy-C₁-C₄-alkyl,    -   heterocyclyl, heterocyclyl-C₁-C₄-alkyl,        heterocyclyl-C₁-C₄-haloalkyl,        heterocyclylcarbonyloxy-C₁-C₄-alkyl,        heterocyclyloxycarbonyl-C₁-C₄-alkyl,        heterocyclyloxy-C₁-C₄-alkyl,    -   where the aforementioned radicals may be partially or fully        halogenated and/or may bear from one to three radicals from the        group of cyano, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy,        hydroxycarbonyl, C₁-C₆-alkoxy-carbonyl, di(C₁-C₆-alkyl)amino,        aryl and aryl(C₁-C₆-alkyl);-   R³ is C₁-C₄-alkyl, preferably methyl; and-   R⁴ is aryl which may be partially or fully halogenated and/or may    bear from one to three radicals from the group of cyano, nitro,    C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, aryl    and aryl(C₁-C₆-alkyl); preferably phenyl or 1-naphthyl.

The amines of the formula II can be cleaved hydrogenolytically to thechiral amines of the formula VIII

where the R¹ and R² radicals are each as defined for the compounds ofthe formula I, by processes known per se.

Typically, this hydrogenolysis is carried out in an inert solvent, forexample an alcohol, such as methanol, ethanol, isopropanol or butanol,an ether, for example tetrahydrofuran, dioxane, a hydrocarbon, forexample benzene, toluene, ethylbenzene or xylene, or mixtures thereof.The hydrogenolysis can be carried out by means of hydrogen in thepresence of a catalytic amount of a platinum group metal element,preferably over Pt/C, Pd/C or Pd/Al₂O₃, more preferably over Pd/C orPd/Al₂O₃. In this case, the hydrogen is generally used in excess. Thereaction is effected generally at from room temperature to refluxtemperature of the reaction mixture and from standard pressure up to apressure of 200 bar. After the reaction has ended, the reaction mixtureis worked up by methods known to those skilled in the art.

However, it is also possible to carry out the hydrogenolysis by means ofmetal hydrides, for example lithium aluminum hydride, sodium boranate,sodium cyanoboranate, diborane etc. In this case, the reactants aregenerally used in a stoichiometric ratio. From case to case, it may alsobe advantageous to use metal hydride in excess. The reaction is effectedgenerally at from room temperature to reflux temperature of the reactionmixture, at standard pressure. After the reaction has ended, thereaction mixture is worked up by methods known to those skilled in theart.

The hydrogenolysis of the amines of the formula II can be carried outcontinuously, semicontinuously or batchwise.

The R¹ and R² radicals of the compounds of the formula I, II, III, VIand VIII and the R^(1′) radical of the compounds of the formula V may,according to the substitution pattern, bear further chiral centers.These compounds too fall within the subject matter of the presentinvention.

The organic molecular moieties specified for the substituents R¹-R⁴ oras radicals on phenyl, aryl, heteroaryl or heterocyclyl rings etc.constitute collective terms for individual lists of the specific groupmembers.

All hydrocarbon chains may be straight or branched.

Unless stated otherwise, halogenated substituents bear preferably fromone to five identical or different heteroatoms. The definition “halogen”in each case represents fluorine, chlorine, bromine or iodine.

Examples of further definitions are:

-   -   aryl: mono- to tricyclic aromatic carbocycle having from 6 to 14        ring members, for example phenyl, naphthyl and anthracenyl,        preferably phenyl, naphthyl;    -   heterocyclyl: monocyclic, saturated or partially unsaturated        hydrocarbons which have from three to six ring members and, as        well as carbon atoms, may comprise from one to four nitrogen        atoms, or from one to three nitrogen atoms and one oxygen or        sulfur atom, or from one to three oxygen atoms, or from one to        three sulfur atoms, and which may be bonded via a carbon atom or        a nitrogen atom, for example.    -   e.g. 2-oxiranyl, 2-oxetanyl, 3-oxetanyl, 2-aziridinyl,        3-thiethanyl, 1-azetidinyl, 2-azetidinyl,    -   e.g. 2-tetrahydrofuranyl, 3-tetrahydrofuranyl,        2-tetrahydrothienyl, 3-tetra-hydrothienyl, 2-pyrrolidinyl,        3-pyrrolidinyl, 3-isoxazolidinyl, 4-isoxazolidinyl,        5-isoxazolidinyl, 3-isothiazolidinyl, 4-isothiazolidinyl,        5-isothiazolidinyl, 3-pyrazolidinyl, 4-pyrazolidinyl,        5-pyrazolidinyl, 2-oxazolidinyl, 4-oxazolidinyl, 5-oxazolidinyl,        2-thiazolidinyl, 4-thiazolidinyl, 5-thiazolidinyl,        2-imidazolidinyl, 4-imidazolidinyl, 1,2,4-oxadiazolidin-3-yl,        1,2,4-oxadiazolidin-5-yl, 1,2,4-thiadiazolidin-3-yl,        1,2,4-thiadiazolidin-5-yl, 1,2,4-triazolidin-3-yl,        1,3,4-oxadiazolidin-2-yl, 1,3,4-thiadiazolidin-2-yl,        1,3,4-triazolidin-2-yl, 1,2,3,4-tetrazolidin-5-yl;    -   e.g. 1-pyrrolidinyl, 2-isothiazolidinyl, 2-isothiazolidinyl,        1-pyrazolidinyl, 3-oxazolidinyl, 3-thiazolidinyl,        1-imidazolidinyl, 1,2,4-triazolidin-1-yl,        1,2,4-oxadiazolidin-2-yl, 1,2,4-oxadiazolidin-4-yl,        1,2,4-thiadiazolidin-2-yl, 1,2,4-thiadiazolidin-4-yl,        1,2,3,4-tetrazolidin-1-yl,    -   e.g. 2,3-dihydrofur-2-yl, 2,3-dihydrofur-3-yl,        2,4-dihydrofur-2-yl, 2,4-dihydrofur-3-yl, 2,3-dihydrothien-2-yl,        2,3-dihydrothien-3-yl, 2,4-dihydrothien-2-yl,        2,4-dihydrothien-3-yl, 4,5-dihydropyrrol-2-yl,        4,5-dihydropyrrol-3-yl, 2,5-dihydropyrrol-2-yl,        2,5-dihydropyrrol-3-yl, 4,5-dihydroisoxazol-3-yl,        2,5-dihydroisoxazol-3-yl, 2,3-di-hydroisoxazol-3-yl,        4,5-dihydroisoxazol-4-yl, 2,5-dihydroisoxazol-4-yl,        2,3-dihydro-isoxazol-4-yl, 4,5-dihydroisoxazol-5-yl,        2,5-dihydroisoxazol-5-yl, 2,3-dihydro-isoxazol-5-yl,        4,5-dihydroisothiazol-3-yl, 2,5-dihydroisothiazol-3-yl,        2,3-dihydro-isothiazol-3-yl, 4,5-dihydroisothiazol-4-yl,        2,5-dihydroisothiazol-4-yl, 2,3-dihydro-isothiazol-4-yl,        4,5-dihydroisothiazol-5-yl, 2,5-dihydroisothiazol-5-yl,        2,3-dihydro-isothiazol-5-yl, 2,3-dihydropyrazol-2-yl,        2,3-dihydropyrazol-3-yl, 2,3-dihydropyrazol-4-yl,        2,3-dihydropyrazol-5-yl, 3,4-dihydropyrazol-3-yl,        3,4-dihydropyrazol-4-yl, 3,4-dihydropyrazol-5-yl,        4,5-dihydropyrazol-3-yl, 4,5-dihydropyrazol-4-yl,        4,5-dihydropyrazol-5-yl, 2,3-dihydroimidazol-2-yl,        2,3-dihydroimidazol-3-yl, 2,3-di-hydroimidazol-4-yl,        2,3-dihydroimidazol-5-yl, 4,5-dihydroimidazol-2-yl,        4,5-di-hydroimidazol-4-yl, 4,5-dihydroimidazol-5-yl,        2,5-dihydroimidazol-2-yl, 2,5-di-hydroimidazol-4-yl,        2,5-dihydroimidazol-5-yl, 2,3-dihydrooxazol-3-yl,        2,3-dihydro-oxazol-4-yl, 2,3-dihydrooxazol-5-yl,        3,4-dihydrooxazol-3-yl, 3,4-dihydrooxazol-4-yl,        3,4-dihydrooxazol-5-yl, 2,3-dihydrothiazol-3-yl,        2,3-dihydrothiazol-4-yl, 2,3-di-hydrothiazol-5-yl,        3,4-dihydrothiazol-3-yl, 3,4-dihydrothiazol-4-yl,        3,4-dihydrothiazol-5-yl, 3,4-dihydrothiazol-2-yl,        3,4-dihydrothiazol-3-yl, 3,4-dihydrothiazol-4-yl,    -   e.g. 4,5-dihydropyrrol-1-yl, 2,5-dihydropyrrol-1-yl,        4,5-dihydroisoxazol-2-yl, 2,3-dihydroisoxazol-1-yl,        4,5-dihydroisothiazol-1-yl, 2,3-dihydroisothiazol-1-yl,        2,3-di-hydropyrazol-1-yl, 4,5-dihydropyrazol-1-yl,        3,4-dihydropyrazol-1-yl, 2,3-dihydro-imidazol-1-yl,        4,5-dihydroimidazol-1-yl, 2,5-dihydroimidazol-1-yl,        2,3-dihydrooxazol-2-yl, 3,4-dihydrooxazol-2-yl,        2,3-dihydrothiazol-2-yl, 3,4-dihydrothiazol-2-yl;    -   e.g. 2-piperidinyl, 3-piperidinyl, 4-piperidinyl,        1,3-dioxan-2-yl, 1,3-dioxan-4-yl, 1,3-dioxan-5-yl,        1,4-dioxan-2-yl, 1,3-dithian-2-yl, 1,4-dithian-3-yl,        1,3-dithian-4-yl, 1,4-dithian-2-yl, 2-tetrahydropyranyl,        3-tetrahydropyranyl, 4-tetrahydropyranyl,        2-tetrahydrothiopyranyl, 3-tetrahydrothiopyranyl,        4-tetrahydrothiopyranyl, 3-hexahydropyridazinyl,        4-hexahydropyridazinyl, 2-hexahydropyrimidinyl,        4-hexahydropyrimidinyl, 5-hexahydropyrimidinyl, 2-piperazinyl,        1,3,5-hexa-hydrotriazin-2-yl, 1,2,4-hexahydrotriazin-3-yl,        tetrahydro-1,3-oxazin-2-yl, tetrahydro-1,3-oxazin-6-yl,        2-morpholinyl, 3-morpholinyl, 1,3,5-trioxan-2-yl;    -   e.g. 1-piperidinyl, 1-hexahydropyridazinyl,        1-hexahydropyrimidinyl, 1-piperazinyl,        1,3,5-hexahydrotriazin-1-yl, 1,2,4-hexahydrotriazin-1-yl,        tetrahydro-1,3-oxazin-1-yl, 1-morpholinyl;    -   e.g. 2H-pyran-2-yl, 2H-pyran-3-yl, 2H-pyran-4-yl, 2H-pyran-5-yl,        2H-pyran-6-yl, 3,6-dihydro-2H-pyran-2-yl,        3,6-dihydro-2H-pyran-3-yl, 3,6-dihydro-2H-pyran-4-yl,        3,6-dihydro-2H-pyran-5-yl, 3,6-dihydro-2H-pyran-6-yl,        3,4-dihydro-2H-pyran-3-yl, 3,4-dihydro-2H-pyran-4-yl,        3,4-dihydro-2H-pyran-6-yl, 2H-thiopyran-2-yl, 2H-thiopyran-3-yl,        2H-thiopyran-4-yl, 2H-thiopyran-5-yl, 2H-thiopyran-6-yl,        5,6-dihydro-4H-1,3-oxazin-2-yl;    -   and heteroaryl.    -   Heteroaryl: mono- or bicyclic aromatic heteroaryl which has from        5 to 10 ring members and, as well as carbon atoms, comprises        from 1 to 4 nitrogen atoms, or from 1 to 3 nitrogen atoms and        one oxygen or one sulfur atom, or one oxygen or one sulfur atom,    -   e.g. monocycles such as furyl (e.g. 2-furyl, 3-furyl), thienyl        (e.g. 2-thienyl, 3-thienyl), pyrrolyl (e.g. pyrrol-2-yl,        pyrrol-3-yl), pyrazolyl (e.g. pyrazol-3-yl, pyrazol-4-yl),        isoxazolyl (e.g. isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl),        isothiazolyl (e.g. isothiazol-3-yl, isothiazol-4-yl,        isothiazol-5-yl), imidazolyl (e.g. imidazol-2-yl,        imidazol-4-yl), oxazolyl (e.g. oxazol-2-yl, oxazol-4-yl,        oxazol-5-yl), thiazolyl (e.g. thiazol-2-yl, thiazol-4-yl,        thiazol-5-yl), oxadiazolyl (e.g. 1,2,3-oxadiazol-4-yl,        1,2,3-oxadiazol-5-yl, 1,2,4-oxadiazol-3-yl,        1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl), thiadiazolyl (e.g.        1,2,3-thiadiazol-4-yl, 1,2,3-thiadiazol-5-yl,        1,2,4-thiadiazol-3-yl, 1,2,4-thiadiazol-5-yl,        1,3,4-thiadiazolyl-2-yl), triazolyl (e.g. 1,2,3-triazol-4-yl,        1,2,4-triazol-3-yl), tetrazol-5-yl, pyridyl (e.g. pyridin-2-yl,        pyridin-3-yl, pyridin-4-yl), pyrazinyl (e.g. pyridazin-3-yl,        pyridazin-4-yl), pyrimidinyl (e.g. pyrimidin-2-yl,        pyrimidin-4-yl, pyrimidin-5-yl), pyrazin-2-yl, triazinyl (e.g.        1,3,5-triazin-2-yl, 1,2,4-triazin-3-yl, 1,2,4-triazin-5-yl,        1,2,4-triazin-6-yl), tetrazinyl (e.g. 1,2,4,5-tetrazin-3-yl);        and also    -   bicycles such as the benzofused derivatives of the        aforementioned monocycles, e.g. quinolinyl, isoquinolinyl,        indolyl, benzothienyl, benzofuranyl, benzoxazolyl,        benzothiazolyl, benzisothiazolyl, benzimidazolyl,        benzopyrazolyl, benzothiadiazolyl, benzotriazolyl;    -   preferably    -   5- or 6-membered heteroaryl having from one to four nitrogen        atoms, or from one to three nitrogen atoms and one oxygen or        sulfur atom, or having one oxygen or sulfur atom:    -   e.g. aromatic 5-membered heterocyclic rings which are bonded via        a carbon atom and, as well as carbon atoms, may comprise from        one to four nitrogen atoms, or from one to three nitrogen atoms        and one sulfur or oxygen atom, or one sulfur or oxygen atom as        ring members, e.g. 2-furyl, 3-furyl, 2-thienyl, 3-thienyl,        2-pyrrolyl, 3-pyrrolyl, 3-isoxazolyl, 4-isoxazolyl,        5-isoxazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl,        3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 2-oxazolyl, 4-oxazolyl,        5-oxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-imidazolyl,        4-imidazolyl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl,        1,2,4-thiadiazol-3-yl, 1,2,4-thiadiazol-5-yl,        1,2,4-triazol-3-yl, 1,3,4-oxadiazol-2-yl, 1,3,4-thiadiazol-2-yl        and 1,3,4-triazol-2-yl;    -   e.g. aromatic 6-membered heterocyclic rings which are bonded via        a carbon atom and, as well as carbon atoms, may comprise from        one to four, preferably from one to three nitrogen atoms as ring        members, e.g. 2-pyridinyl, 3-pyridinyl, 4-pyridinyl,        3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl,        5-pyrimidinyl, 2-pyrazinyl, 1,3,5-triazin-2-yl and        1,2,4-triazin-3-yl.

EXAMPLES

The copper-containing catalysts used in the examples which follow wereprepared as described in the following documents:

DE 19826396, DE 4428004, EP 383132 and DE 3717111

The diastereomeric ratio of the compounds prepared in examples I and IIwhich follow was determined as follows: derivatization withtrifluoroacetic acid, gas chromatography separation on BGB 175 column.

The diastereomeric ratio of the compounds prepared in examples III andVI which follow was determined as follows: derivatization withtrifluoroacetic acid, gas chromatography separation on Hydrodex beta6-TBDM column.

The diastereomeric ratio of the compounds prepared in example VII whichfollows was determined as follows: gas chromatography separation onCP-SIL 19 CB column.

The diastereomeric ratio of the compounds prepared in example VIII whichfollows was determined as follows: gas chromatography separation onOV1701 column.

The diastereomeric ratio of the compounds prepared in example IX whichfollows was determined as follows: gas chromatography separation onRTX-5-Amine column.

I. General Method A Diaselective Hydrogenation of(R)-Sec-Butylidene(1-Phenyl-Ethyl)Amine (Schiff Base of(R)-(1-Phenylethyl)Amine with 2-Butanone)

540 mg of catalyst were introduced into a 15 ml autoclave and inertizedwith nitrogen. Subsequently, the catalyst was preactivated at a pressureof 50 bar at the temperature specified in table 1 with hydrogen for 2hours. This was then followed by purging with nitrogen, cooling to roomtemperature at the same time, and then addition under nitrogen of amixture of 5.97 ml of (R)-sec-butylidene(1-phenylethyl)amine and 1.03 mlof methanol. Subsequently, hydrogen was injected until a pressure ofabout 20 bar was attained and the reaction mixture was heated to 100° C.On attainment of this temperature, the pressure was increased to 70 barwith hydrogen and the stirrer was started at 1000 rpm. After 6 hoursunder these reaction conditions, a sample was taken and was analyzed bygas chromatography. The results are reported in table 1 below.

TABLE 1 Catalyst Conversion [metal loading Activation [based on RR/RSExample in % by wt.] Support [° C.] imine] ratio 1.1 Cu/Ni (5/5) TiO₂200 91 84/16 1.2 Cu/Ni (5/5) TiO₂ 300 >99 82/18 1.3 Cu/Ni/Mo ZrO₂ 200 9985/15 (13/40/1) 1.4 Cu/Co (5/5) TiO₂ 200 >99 84/16 1.5 Cu/Co (5/5) TiO₂300 >99 84/16 1.6 Cu/Ni/Co TiO₂ 200 98 83/17 (3.3/3.3/3.3) 1.7 Cu/Ni/CoTiO₂ 300 >99 85/15 (3.3/3.3/3.3) 1.8 Cu/Ni/Co ZrO₂ 200 99 85/15(11/21/21) 1.9 Cu/Zn (32/32) Al₂O₃ 200 98 83/17

For comparison, under the same conditions, the reaction was carried outwith an unsupported iron catalyst (100% iron oxide), a copper ontitanium dioxide catalyst, a nickel on titanium dioxide catalyst and anickel/cobalt on titanium dioxide catalyst. The results are listed intable 2.

TABLE 2 Comparative examples Catalyst Conversion [metal loadingActivation [based on RR/RS Example in % by wt.] Support [° C.] imine]ratio 2.1 Fe — 200 10 59/41 2.2 Cu (10) TiO₂ 200 23 76/24 2.3 Cu (10)TiO₂ 300 21 78/22 2.4 Ni (10) TiO₂ 200 >99 75/25 2.5 Co (10) TiO₂ 200 9983/15 2.6 Ni/Co (5/5) TiO₂ 200 90 77/23 2.7 Ni/Co (5/5) TiO₂ 300 >9975/25

Comparison of the results from tables 1 and 2 shows clearly that theaddition of copper to the particular non-copper-containing catalystsbrings about an increase in the diastereoselectivity.

II. General Method B Diaselective Hydrogenation of(R)-Sec-Butylidene(1-Phenyl-Ethyl)Amine (Schiff Base of(R)-(1-Phenylethyl)Amine with 2-Butanone)

A mixture of (R)-sec-butylidene(1-phenylethyl)amine (imine); solvent andpassivated catalyst, as specified in table 3, was initially charged ineach case in a 300 ml autoclave. Subsequently, the mixture was inertizedwith nitrogen and heated to 100° C. Subsequently, at this temperature,hydrogen was injected up to the desired pressure, as likewise specifiedin each case in table 3, and, when the internal pressure declined,brought back to the desired pressure. After the run times specified intable 3 in each case, measured from injection of hydrogen, a sample wastaken and was analyzed by gas chromatography. The results are reportedin table 3 below.

TABLE 3 % by Catalyst Cat.: wt. of Conversion [metal imine imine Run[based Imine loading in [% by in p time on RR/RS Example [g] % by wt.]Support wt.] Solvent solvent [bar] [h] imine] ratio 3.1 41 Cu/Ni/Co TiO₂2.4 methanol 6 70 6 95 92/8 (3.3/3.3/3.3) 3.2 110 Cu/Ni/Co ZrO₂ 3 ethyl-60 70 12 >99 91/9 (11/21/21) benzene 3.3 110 Cu/Ni/Co ZrO₂ 3 methanol 6070 12 >99 91/9 (11/21/21) 3.4 110 Cu/Ni/Mo ZrO₂ 3 ethyl- 60 70 12 >9991/9 (13/40/1) benzene 3.5 110 Cu/Ni/Mo ZrO₂ 3 methanol 60 70 12 >9991/9 (13/40/1) 3.6 11 Cu/Ni/Mo ZrO₂ 1 methanol 8.5 100 24 >99 91/9(13/40/1)

For example, under the same conditions, the reaction was carried outwith a Pt/C catalyst. The results are listed in table 4. The exampleshows that the inventive tests exhibit a higher diaselectivity.

TABLE 4 Comparative example % by Catalyst Cat.: wt. of Conversion [metalimine imine Run [based Imine loading in [% by in p time on RR/RS Example[g] % by wt.] Support wt.] Solvent solvent [bar] [h] imine] ratio 4.1 11Pt (10) C 1 methanol 8.5 100 24 >99 80/20

III. General Method C Diaselective Hydrogenation of(R)-1,2-Dimethyl-Propylidene(Phenylethyl)Amine (Schiff Base of(R)-(1-Phenylethyl)Amine with 3-Methyl-2-Butanone)

540 mg of catalyst were added to a 15 ml autoclave and inertized withnitrogen. Subsequently, the catalyst was preactivated with hydrogen at apressure of 50 bar at the temperature specified in table 5 for 2 hours.This was then followed by purging with nitrogen, cooling to roomtemperature at the same time, and then addition under nitrogen of amixture of 6.0 ml of (R)-1,2-dimethylpropylidene(1-phenylethyl)amine and1.0 ml of ethylbenzene. Subsequently, hydrogen was injected until apressure of about 20 bar was attained and the reaction mixture washeated to 100° C. On attainment of this temperature, the pressure wasincreased to 70 bar with hydrogen and the stirrer was started at 1000rpm. After 3 hours under these reaction conditions, a sample was takenand was analyzed by gas chromatography. The results are reported intable 5 below.

TABLE 5 Conversion Catalyst Activation [based on RR/RS Example [metalloading in %] Support [° C.] imine] ratio 5.1 Cu/Ni (5/5) TiO₂ 200 7294/6 5.2 Cu/Ni/Mo (13/40/1) ZrO₂ 200 >99 98/2 5.3 Cu/Co (5/5) TiO₂ 20080 98/2 5.4 Cu/Co/Mn/Mo/P unsupported 200 13 98/2 (20/50/7/3/3) 5.5Cu/Co/Mn/Mo/P unsupported 300 20 98/2 (20/50/7/3/3) 5.6 Cu/Ni/Co(3.3/3.3/3.3) TiO₂ 300 88 98/2 5.7 Cu/Ni/Co (11/21/21) ZrO₂ 200 95 98/25.8 Cu/Zn (32/32) Al₂O₃ 200 49 98/2

For comparison, under the same conditions, the reaction was carried outwith an unsupported iron catalyst. The results are listed in table 6.All examples show that the inventive tests exhibit a higherdiaselectivity.

TABLE 6 Comparative examples Catalyst Conversion [metal Activation[based on RR/RS Example loading in %] Support [° C.] imine] ratio 6.1 Fe(10) TiO₂ 200 5 62/38 6.2 Fe (10) TiO₂ 300 5 66/34 6.3 Cu (10) TiO₂ 2006 91/9  6.4 Ni (10) TiO₂ 200 78 91/9 

IV. General Method D Diaselective Hydrogenation of(R)-1,2-Dimethyl-Propylidene(Phenylethyl)Amine (Schiff Base of(R)-(1-Phenylethyl)Amine with 3-Methyl-2-Butanone)

A mixture of (R)-1,2-dimethylpropylidene(1-phenylethyl)amine (imine),solvent and passivated catalyst, as specified in table 7, was initiallycharged in each case in an autoclave. Subsequently, the mixture wasinertized with nitrogen and heated to the desired temperature.Subsequently, at this temperature, hydrogen was injected up to thedesired pressure, as likewise specified in each case in table 7, and,when the internal pressure declined, brought back to the desiredpressure. After the run times specified in table 7 in each case,measured from injection of hydrogen, a sample was taken and was analyzedby gas chromatography. The results are reported in table 7 below.

TABLE 7 % Catalyst by wt. [metal Catalyst: of imine Autoclave ConversionImine loading in imine in size T p Run [based on RR/RS Example [g] %]Support [% by wt.] Solvent solvent [ml] [° C.] [bar] time [h] imine]ratio 7.1 2000 Cu/Ni/Co ZrO₂ 10 ethylbenzene 50 9000  120 100 42 >9999/1 (11/21/21) 7.2 40 Cu/Ni/Co TiO₂ 2.5 methanol 6 300 100 70 6 63 94/6(3.3/3.3/3.3) 7.3 95 Cu/Ni/Co ZrO₂ 1.5 methanol 60 300 100 70 12 >9999/1 (11/21/21) 7.4 6800 Cu/Ni/Co ZrO₂ 7.5 toluene/ 63 20 000   120 10048 >99 98/2 (11/21/21) ethylbenzene

V. General Method E Diaselective Hydrogenation of(R)-1,2-Dimethylpropylidene-(1-Phenylethyl)Amine (Schiff Base of(R)-(1-Phenylethyl)Amine with 3-Methyl-2-Butanone)

A 250 ml loop reactor (length=48.5 cm, diameter=2.5 cm, fill height=46.5cm), which was operated continuously, was initially charged with apassivated Cu/Ni/Co catalyst on ZrO₂ with a metal loading of 11/21/21%by weight based on the total weight of the catalyst, and a 30% by weightsolution of (R)-1,2-dimethylpropylidene(1-phenyl-ethyl)amine in thesolvent specified in table 8 was hydrogenated with hydrogen under thereaction conditions specified in table 8 in continuous mode. A samplewas taken from the output and analyzed by gas chromatography. Theresults from this are listed in table 8.

TABLE 8 Loading Conversion [g/h * g T p [based on RR/RS Example Solventcat] [° C.] [bar] imine] ratio 8.1 ethylbenzene 0.05 100 100 >99 98/28.2 ethylbenzene 0.07 100 100 >99 98/2 8.3 ethylbenzene 0.05 80 100 >9998/2 8.4 ethylbenzene 0.05 60 100 >99 98/2 8.5 ethylbenzene 0.05 40100 >99 98/2 8.6 ethylbenzene 0.05 40 70 >99 98/2 8.7 ethylbenzene 0.0550 70 >99 98/2 8.8 ethylbenzene 0.05 50 50 >99 98/2 8.9 ethylbenzene0.09 50 50 97 98/2 8.10 ethylbenzene 0.09 70 50 98 98/2 8.11ethylbenzene 0.09 70 70 >99 98/2 8.12 ethylbenzene 0.09 100 100 >99 98/28.13 ethylbenzene 0.14 100 100 >99 98/2 8.14 ethylbenzene 0.18 100100 >99 98/2 8.15 ethylbenzene 0.18 80 100 >99 98/2 8.16 methanol 0.04100 100 >99 98/2 8.17 methanol 0.06 100 100 >99 98/2 8.18 methanol 0.09100 100 >99 98/2 8.19 methanol 0.04 100 70 >99 98/2 8.20 methanol 0.04100 50 >99 98/2 8.21 methanol 0.04 80 50 >99 98/2 8.22 methanol 0.04 6050 >99 98/2 8.23 methanol 0.04 40 50 >99 98/2

VI. General Method F Diaselective Hydrogenation of(S)-1,2-Dimethylpropylidene-(1-Phenylethyl)Amine (Schiff Base of(S)-(1-Phenylethyl)Amine with 3-Methyl-2-Butanone)

A 250 ml loop reactor (length=48.5 cm, diameter=2.5 cm, fill height=46.5cm), which was operated continuously, was initially charged with apassivated Cu/Ni/Mo catalyst on ZrO₂ with a metal loading of 13/40/1% byweight based on the total weight of the catalyst, and a 30% by weightsolution of (S)-1,2-dimethylpropylidene(1-phenyl-ethyl)amine in methanolwas hydrogenated with hydrogen under the reaction conditions specifiedin table 9 in continuous mode. A sample was taken from the output andanalyzed by gas chromatography. The results from this are listed intable 9.

TABLE 9 Loading T p Conversion SS/SR Example [g/h * g cat] [° C.] [bar][based on imine] ratio 9.1 0.06 100 120 99 95/5 9.2 0.10 100 120 99 95/59.3 0.19 100 120 98 95/5 9.4 0.16 100 100 >99 96/4 9.5 0.16 90 100 >9996/4 9.6 0.16 80 100 >99 96/4 9.7 0.19 100 120 98 95/5 9.8 0.25 100 12097 95/5

VII. General Method G Diaselective Hydrogenation of(R)-(1-Cyclopropylidene)(1-Phenylethyl)Amine (Schiff Base of(R)-(1-Phenylethyl)Amine with 1-Cyclopropyl-1-Ethanone)

315 mg of catalyst were introduced into a 15 ml autoclave and inertizedwith nitrogen. Subsequently, the catalyst was preactivated with hydrogenat a pressure of 50 bar at the temperature specified in table 10 for 2hours. This was then followed by purging with nitrogen, cooling to roomtemperature at the same time, and then addition under nitrogen of amixture of 3.5 ml of (R)-(1-cyclopropylidene)(1-phenylethyl)amine and3.5 ml of ethylbenzene. Subsequently, hydrogen was injected until apressure of about 20 bar was attained and the reaction mixture washeated to 100° C. On attainment of this temperature, the pressure wasincreased to 70 bar with hydrogen and the stirrer was started at 1000rpm. After 3 hours under these reaction conditions, a sample was takenand was analyzed by gas chromatography. The results are reported intable 10 below.

TABLE 10 Catalyst [metal loading in % Activation Conversion RR/RSExample by wt.] Support [° C.] [based on imine] ratio 10.1 Cu/Ni/Mo(13/40/1) ZrO₂ 200 94 67/33 10.2 Cu/Co/Mn/Mo/P unsupported 300 32 67/33(20/50/7/3/3) 10.3 Cu/Ni/Co TiO₂ 300 62 67/33 (3.3/3.3/3.3) 10.4Cu/Ni/Co (11/21/21) ZrO₂ 200 99 67/33 10.5 Cu/Zn(32/32) Al₂O₃ 200 8964/36

For comparison, under the same conditions, the reaction was carried outwith a nickel/cobalt on titanium dioxide catalyst. The results arelisted in table 11.

TABLE 11 Comparative examples Catalyst [metal RR/ loading in ActivationConversion RS Example % by wt.] Support [° C.] [based on imine] ratio11.1 Ni/Co (5/5) TiO₂ 300 30 67/33

Comparison of the results from tables 10 and 11 shows clearly that theaddition of copper to the particular non-copper-containing catalysts ahigher conversion can be achieved at comparable diastereoselectivity.

VIII. General Method H Diaselective Hydrogenation of(R)-(1-Phenylethylidene)(1-Phenylethyl)Amine (Schiff Base of(R)-(1-Phenylethyl)Amine with 1-Phenyl-1-Ethanone

315 mg of catalyst were introduced into a 15 ml autoclave and inertizedwith nitrogen. Subsequently, the catalyst was preactivated with hydrogenat a pressure of 50 bar at the temperature specified in table 12 for 2hours. This was then followed by purging with nitrogen, cooling to roomtemperature at the same time, and then addition under nitrogen of amixture of 3.5 ml of (R)-(1-phenylethylidene)(1-phenylethyl)amine and3.5 ml of ethylbenzene. Subsequently, hydrogen was injected until apressure of about 20 bar was attained and the reaction mixture washeated to 100° C. On attainment of this temperature, the pressure wasincreased to 70 bar with hydrogen and the stirrer was started at 1000rpm. After 3 hours under these reaction conditions, a sample was takenand was analyzed by gas chromatography. The results are reported intable 12 below.

TABLE 12 Catalyst Conversion [metal loading in % Activation [based onRR/RS Example by wt.] Support [° C.] imine] ratio 12.1 Cu/Ni/Mo(13/40/1) ZrO₂ 200 >99 94/6 12.2 Cu/Co/Mn/Mo/P unsupported 300 53 98/2(20/50/7/3/3) 12.3 Cu/Ni/Co (3.3/3.3/3.3) TiO₂ 300 48 98/2 12.4 Cu/Ni/Co(11/21/21) ZrO₂ 200 >99 98/2 12.5 Cu/Zn(32/32) Al₂O₃ 200 >99 99/1

For comparison, under the same conditions, the reaction was carried outwith a copper on titanium dioxide and a nickel/cobalt on titaniumdioxide catalyst. The results are listed in table 13.

TABLE 13 Comparative examples Catalyst Conversion [metal loadingActivation [based on RR/RS Example in % by wt.] Support [° C.] imine]ratio 13.1 Cu (10) TiO₂ 200 1 75/25 13.2 Ni/Co (5/5) TiO₂ 300 47 96/4 

Comparison of the results of tables 12 and 13 shows clearly that theaddition of copper to the particular non-copper-containing catalystsleads to an increase in the diastereoselectivity.

IX. General Method I Diaselective Hydrogenation of(R)-1-Phenylbutylidene(1-Phenylethyl)Amine (Schiff Base of(R)-(1-Phenylethyl)Amine with 1-Phenyl-1-Butanone)

A mixture of 35% by weight of (R)-1-phenylbutylidene(1-phenylethyl)amine(imine) in methanol and passivated catalyst, as specified in table 14,was initially charged in each case in a 300 ml autoclave. This wasfollowed by inertization with nitrogen and heating to 100° C.Subsequently, hydrogen was injected at this temperature up to a pressureof 100 bar and, when the internal pressure declined, brought back to thedesired pressure. After 24 hours, measured from the injection ofhydrogen, a sample was taken and was analyzed by gas chromatography. Theresults are reported in table 14 below.

TABLE 14 Conversion Imine Catalyst Catalyst: imine [based on RR/RSExample [g] [metal loading in %] Support [% by wt.] imine] ratio 14.1 48Cu/Ni/Co (11/21/21) ZrO₂ 5 98 98/2 14.2 48 Cu/Ni/Mo (13/40/1) ZrO₂ 5 9898/2

X. General Method J Synthesis of the Imines

The imines (Schiff bases) can be synthesized by a modified method ofCharles et al., Bull. Soc. Chim. Fr. 1970, 12, 4439-4446.

The ketone is initially charged with 1.25 eq. of your enantiomer of(1-phenylethyl)amine and 0.01 eq. of p-toluenesulfonic acid in toluene.The water of reaction which forms is removed continuously by means ofazeotropic distillation. When no further conversion can be discerned bymeans of GC, the solvent is drawn off and the product is purified bymeans of a fractional distillation.

1. A process, comprising diastereoselectively converting a chiral imineof formula I to an amine of formula II

where R¹, R² are each C₁-C₆-alkyl, C₃-C₆-cycloalkyl, C₂-C₆-alkenyl,C₂-C₆-alkynyl, C₂-C₆-haloalkenyl, C₂-C₆-haloalkynyl,C₁-C₆-alkoxycarbonyl, C₃-C₆-alkenyloxy-carbonyl,C₃-C₆-alkynyloxycarbonyl, aminocarbonyl, C₁-C₆-alkylaminocarbonyl,C₃-C₆-alkenylaminocarbonyl, C₃-C₆-alkynylamino-carbonyl,C₁-C₆-alkylsulfonylaminocarbonyl, di(C₁-C₆-alkyl)aminocarbonyl,N-(C₃-C₆-alkenyl)-N-(C₁-C₆-alkyl)aminocarbonyl,N-(C₃-C₆-alkynyl)-N-(C₁-C₆-alkyl)aminocarbonyl,N-(C₁-C₆-alkoxy)-N-(C₁-C₆-alkyl)aminocarbonyl,N-(C₃-C₆-alkenyl)-N-(C₁-C₆-alkoxy)aminocarbonyl,N-(C₃-C₆-alkynyl)-N-(C₁-C₆-alkoxy)aminocarbonyl,(C₁-C₆-alkyl)aminothiocarbonyl, di(C₁-C₆-alkyl)aminothiocarbonyl orC₁-C₆-alkylcarbonyl-C₁-C₆-alkyl, where the alkyl, cycloalkyl and alkoxyradicals mentioned are optionally partially or fully halogenated andoptionally have from one to three of: cyano, hydroxyl, C₁-C₄-alkyl,C₃-C₆-cycloalkyl, C₁-C₆-alkoxy-C₁-C₄-alkyl,C₁-C₄-alkoxy-C₁-C₄-alkoxy-C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-alkylthio,amino, C₁-C₄-alkylamino, di(C₁-C₄-alkyl)amino, C₁-C₄-alkylcarbonylamino,hydroxycarbonyl, C₁-C₄-alkoxycarbonyl, aminocarbonyl,C₁-C₄-alkylaminocarbonyl, di(C₁-C₄-alkyl)aminocarbonyl orC₁-C₄-alkylcarbonyloxy; aryl, aryl-C₁-C₄-alkyl, aryl-C₂-C₄-alkenyl,aryl-C₂-C₄-alkynyl, aryl-C₁-C₄-haloalkyl, aryl-C₂-C₄-haloalkenyl,aryl-C₃-C₄-haloalkynyl, aryl-C₁-C₄-hydroxyalkyl,arylcarbonyl-C₁-C₄-alkyl, aryl-C₁-C₄-alkylcarbonyl-C₁-C₄-alkyl,arylcarbonyloxy-C₁-C₄-alkyl, aryloxycarbonyl-C₁-C₄-alkyl,aryloxy-C₁-C₄-alkyl, arylamino-C₁-C₄-alkyl, arylthio-C₁-C₄-alkyl,arylsulfinyl-C₁-C₄-alkyl, arylsulfonyl-C₁-C₄-alkyl, heterocyclyl,heterocyclyl-C₁-C₄-alkyl, heterocyclyl-C₂-C₄-alkenyl,heterocyclyl-C₂-C₄-alkynyl, heterocyclyl-C₁-C₄-haloalkyl,heterocyclyl-C₂-C₄-haloalkenyl, heterocyclyl-C₃-C₄-haloalkynyl,heterocyclyl-C₁-C₄-hydroxyalkyl, heterocyclylcarbonyl-C₁-C₄-alkyl,heterocyclyl-C₁-C₄-alkyl-carbonyl-C₁-C₄-alkyl,heterocyclylcarbonyloxy-C₁-C₄-alkyl,heterocyclyloxycarbonyl-C₁-C₄-alkyl, heterocyclyloxy-C₁-C₄-alkyl,heterocyclylamino-C₁-C₄-alkyl, heterocyclylthio-C₁-C₄-alkyl,heterocyclylsulfinyl-C₁-C₄-alkyl, heterocyclylsulfonyl-C₁-C₄-alkyl,where the aforementioned radicals are optionally partially or fullyhalogenated and optionally have from one to three radicals from thegroup consisting of cyano, nitro, C₁-C₆-alkyl, C₁-C₆-haloalkyl,hydroxycarbonyl-C₁-C₆-alkyl, C₁-C₄-alkoxycarbonyl-C₁-C₆-alkyl, hydroxyl,C₁-C₆-hydroxyalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, hydroxycarbonyl,C₁-C₆-alkoxycarbonyl, aminocarbonyl, (C₁-C₆-alkyl)aminocarbonyl,di(C₁-C₆-alkyl)aminocarbonyl, hydroxycarbonyl-C₁-C₆-alkoxy,C₁-C₆-alkoxycarbonyl-C₁-C₆-alkoxy, amino, C₁-C₆-alkylamino,di(C₁-C₆-alkyl)amino, C₁-C₆-alkyl-sulfonylamino,C₁-C₆-haloalkylsulfonylamino, (C₁-C_(o)-alkyl)amino-carbonylamino,di(C₁-C₆-alkyl)aminocarbonylamino, aryl and aryl(C₁-C₆-alkyl); where theR¹ and R² radicals are different than one another; R³ is C₁-C₆-alkyl; R⁴is aryl which is optionally partially or fully halogenated andoptionally have from one to three radicals of cyano, nitro, C₁-C₆-alkyl,C₁-C₆-haloalkyl, hydroxyl, C₁-C₆-hydroxyalkyl, C₁-C₆-alkoxy,C₁-C₆-haloalkoxy, hydroxycarbonyl, C₁-C₆-alkoxycarbonyl,C₁-C₆-alkylamino, di(C₁-C₆-alkyl)amino, aryl and aryl(C₁-C₆-alkyl);and * represents a S or R configuration, and ** represents at least oneof S and R configurations; wherein the conversion is carried out in thepresence of hydrogen and a heterogeneous copper-containing catalyst,wherein the heterogeneous copper-containing catalyst comprises, based onthe total weight of the catalyst, 0.1-95% by weight of copper, 0.1-85%by weight of at least one metal selected from the group consisting ofnickel, cobalt and zinc; 0-15% by weight of at least one promoterselected from the group consisting of iron, rhodium, ruthenium,palladium, platinum, iridium, osmium, silver, gold, molybdenum,tungsten, rhenium, cadmium, lead, manganese, tin, chromium, lithium,sodium, potassium, cesium, magnesium, barium, phosphorus, arsenic,antimony, bismuth, selenium and tellurium; where a sum of thepercentages by weight does not exceed 100%.
 2. (canceled)
 3. The processaccording to claim 1, wherein the copper-containing catalyst comprises asupport material.
 4. The process according to claim 1, wherein theheterogeneous copper-containing catalyst comprises, as a supportmaterial, carbon or a porous metal oxide selected from the groupconsisting of aluminum oxide, silicon dioxide, aluminosilicates,titanium dioxide, zirconium dioxide, magnesium oxide or mixturesthereof.
 5. The process according to claim 1, wherein thecopper-containing catalyst is an unsupported catalyst.
 6. The processaccording to claim 1, wherein the conversion is carried out in thepresence of a solvent or in substance.
 7. The process according to claim1, wherein the conversion is carried out at from standard pressure to200 bar.
 8. The process according to claim 1, wherein the conversion iscarried out at from room temperature to reflux temperature of a reactionmixture.
 9. The process according to claim 1, wherein R³ is C₁-C₄-alkyl,and R⁴ is aryl which is optionally partially or fully halogenated andoptionally have from one to three radicals selected from the groupconsisting of cyano, nitro, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy,C₁-C₆-haloalkoxy, aryl and aryl(C₁-C₆-alkyl).
 10. The process accordingto claim 1, wherein R¹, R² are each C₁-C₆-alkyl, C₃-C₆-cycloalkyl,C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₂-C₆-haloalkenyl, C₂-C₆-haloalkynyl orC₁-C₆-alkylcarbonyl-C₁-C₆-alkyl, where the alkyl, cycloalkyl and alkoxyradicals mentioned are optionally partially or fully halogenated andoptionally have from one to three of: cyano, hydroxyl, C₁-C₄-alkyl,C₃-C₆-cycloalkyl, C₁-C₆-alkoxy-C₁-C₄-alkyl,C₁-C₄-alkoxy-C₁-C₄-alkoxy-C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-alkylthio,amino, C₁-C₄-alkylamino, di(C₁-C₄-alkyl)amino; aryl, aryl-C₁-C₄-alkyl,aryl-C₂-C₄-alkenyl, aryl-C₂-C₄-alkynyl, aryl-C₁-C₄-haloalkyl,aryl-C₂-C₄-haloalkenyl, aryl-C₃-C₄-haloalkynyl, aryl-C₁-C₄-hydroxyalkyl,arylcarbonyl-C₁-C₄-alkyl, aryl-C₁-C₄-alkyl, carbonyl-C₁-C₄-alkyl,aryloxy-C₁-C₄-alkyl, arylamino-C₁-C₄-alkyl, arylthio-C₁-C₄-alkyl,arylsulfinyl-C₁-C₄-alkyl, arylsulfonyl-C₁-C₄-alkyl, heterocyclyl,heterocyclyl-C₁-C₄-alkyl, heterocyclyl-C₂-C₄-alkenyl,heterocyclyl-C₂-C₄-alkynyl, heterocyclyl-C₁-C₄-haloalkyl,heterocyclyl-C₂-C₄-haloalkenyl, heterocyclyl-C₃-C₄-haloalkynyl,heterocyclyl-C₁-C₄-hydroxyalkyl, heterocyclylcarbonyl-C₁-C₄-alkyl,heterocyclyl-C₁-C₄-alkylcarbonyl-C₁-C₄-alkyl,heterocyclyloxy-C₁-C₄-alkyl, heterocyclylamino-C₁-C₄-alkyl,heterocyclylthio-C₁-C₄-alkyl, heterocyclylsulfinyl-C₁-C₄-alkyl,heterocyclylsulfonyl-C₁-C₄-alkyl, where the aforementioned radicals areoptionally partially or fully halogenated and optionally have from oneto three radicals selected from the group consisting of cyano, nitro,C₁-C₆-alkyl, C₁-C₆-haloalkyl, hydroxyl, C₁-C₆-hydroxyalkyl,C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, C₁-C₆-alkoxycarbonyl,di(C₁-C₆-alkyl)aminocarbonyl, amino, C₁-C₆-alkylamino,di(C₁-C₆-alkyl)amino, C₁-C₆-alkylsulfonylamino,C₁-C₆-haloalkylsulfonylamino, aryl and aryl(C₁-C₆-alkyl).
 11. A processfor preparing an amine of formula II,

comprising a) reacting a ketone of the formula III with an amine of theformula IV

to obtain an imine of formula I

where R¹, R² are each C₁-C₆-alkyl, C₃-C₆-cycloalkyl, C₂-C₆-alkenyl,C₂-C₆-alkynyl, C₁-C₆-haloalkenyl, C₂-C₆-haloalkynyl,C₁-C₆-alkoxycarbonyl, C₃-C₆-alkenyloxy-carbonyl,C₃-C₆-alkynyloxycarbonyl, aminocarbonyl, C₁-C₆-alkylaminocarbonyl,C₃-C₆-alkenylaminocarbonyl, C₃-C₆-alkynylamino-carbonyl,C₁-C₆-alkylsulfonylaminocarbonyl, di(C₁-C₆-alkyl)aminocarbonyl,N-(C₃-C₆-alkenyl)-N-(C₁-C₆-alkyl)aminocarbonyl,N-(C₃-C₆-alkynyl)-N-(C₁-C₆-alkyl)aminocarbonyl,N-(C₁-C₆-alkoxy)-N-(C₁-C₆-alkyl)aminocarbonyl,N-(C₃-C₆-alkenyl)-N-(C₁-C₆-alkoxy)aminocarbonyl,N-(C₃-C₆-alkynyl)-N-(C₁-C₆-alkoxy)aminocarbonyl,(C₁-C₆-alkyl)aminothiocarbonyl, di(C₁-C₆-alkyl)aminothiocarbonyl orC₁-C₆-alkylcarbonyl-C₁-C₆-alkyl, where the alkyl, cycloalkyl and alkoxyradicals mentioned are optionally partially or fully halogenated andoptionally have from one to three of: cyano, hydroxyl, C₁-C₄-alkyl,C₃-C₆-cycloalkyl, C₁-C₆-alkoxy-C₁-C₄-alkyl,C₁-C₄-alkoxy-C₁-C₄-alkoxy-C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-alkylthio,amino, C₁-C₄-alkylamino, di(C₁-C₄-alkyl)amino, C₁-C₄-alkylcarbonylamino,hydroxycarbonyl, C₁-C₄-alkoxycarbonyl, aminocarbonyl,C₁-C₄-alkylaminocarbonyl, di(C₁-C₄-alkyl)aminocarbonyl orC₁-C₄-alkylcarbonyloxy; aryl, aryl-C₁-C₄-alkyl, aryl-C₇-C₄-alkenyl,aryl-C₂-C₄-alkynyl, aryl-C₁-C₄-haloalkyl, aryl-C₂-C₄-haloalkenyl,aryl-C₃-C₄-haloalkynyl, aryl-C₁-C₄-hydroxyalkyl,arylcarbonyl-C₁-C₄-alkyl, aryl-C₁-C₄-alkylcarbonyl-C₁-C₄-alkyl,arylcarbonyloxy-C₁-C₄-alkyl, aryloxycarbonyl-C₁-C₄-alkyl,aryloxy-C₁-C₄-alkyl, arylamino-C₁-C₄-alkyl, arylthio-C₁-C₄-alkyl,arylsulfinyl-C₁-C₄-alkyl, arylsulfonyl-C₁-C₄-alkyl, heterocyclyl,heterocyclyl-C₁-C₄-alkyl, heterocyclyl-C₂-C₄-alkenyl,heterocyclyl-C₂-C₄-alkynyl, heterocyclyl-C₁-C₄-haloalkyl,heterocyclyl-C₂-C₄-haloalkenyl, heterocyclyl-C₃-C₄-haloalkynyl,heterocyclyl-C₁-C₄-hydroxyalkyl, heterocyclylcarbonyl-C₁-C₄-alkyl,heterocyclyl-C₁-C₄-alkyl-carbonyl-C₁-C₄-alkyl,heterocyclylcarbonyloxy-C₁-C₄-alkyl,heterocyclyloxycarbonyl-C₁-C₄-alkyl, heterocyclyloxy-C₁-C₄-alkyl,heterocyclylamino-C₁-C₄-alkyl, heterocyclylthio-C₁-C₄-alkyl,heterocyclylsulfinyl-C₁-C₄-alkyl, heterocyclylsulfonyl-C₁-C₄-alkyl,where the aforementioned radicals of are partially or fully halogenatedand optionally have from one to three radicals from the group consistingof cyano, nitro, C₁-C₆-alkyl, C₁-C₆-haloalkyl,hydroxycarbonyl-C₁-C₆-alkyl, C₁-C₄-alkoxycarbonyl-C₁-C₆-alkyl, hydroxyl,C₁-C₆-hydroxyalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, hydroxycarbonyl,C₁-C₆-alkoxycarbonyl, aminocarbonyl, (C₁-C₆-alkyl)aminocarbonyl,di(C₁-C₆-alkyl)aminocarbonyl, hydroxycarbonyl-C₁-C₆-alkoxy,C₁-C₆-alkoxycarbonyl-C₁-C₆-alkoxy, amino, C₁-C₆-alkylamino,di(C₁-C₆-alkyl)amino, C₁-C₆-alkylsulfonylamino,C₁-C₆-haloalkyl-sulfonylamino, (C₁-C₆-alkyl)aminocarbonylamino,di(C₁-C₆-alkyl)-aminocarbonylamino, aryl and aryl(C₁-C₆-alkyl); wherethe R¹ and R² radicals are different than one another; R³ isC₁-C₆-alkyl; R⁴ is aryl which is optionally partially or fullyhalogenated and optionally have from one to three radicals from thegroup consisting of cyano, nitro, C₁-C₆-alkyl, C₁-C₆-haloalkyl,hydroxyl, C₁-C₆-hydroxyalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy,hydroxycarbonyl, C₁-C₆-alkoxycarbonyl, C₁-C₆-alkylamino,di(C₁-C₆-alkyl)amino, aryl and aryl(C₁-C₆-alkyl); and * represents a Sor R configuration, and ** represents at least one of S and Rconfigurations; and then b) reacting the imine of the formula I obtainedfrom a) with hydrogen and a heterogeneous copper-containing catalyst,where the heterogeneous copper-containing catalyst comprises, based onthe total weight of the catalyst, 0.1-95% by weight of copper, 0.1-85%by weight of at least one metal selected from the group of nickel,cobalt and zinc; 0-15% by weight of at least one promoter selected fromthe group of iron, rhodium, ruthenium, palladium, platinum, iridium,osmium, silver, gold, molybdenum, tungsten, rhenium, cadmium, lead,manganese, tin, chromium, lithium, sodium, potassium, cesium, magnesium,barium, phosphorus, arsenic, antimony, bismuth, selenium and tellurium;where a sum of the percentages by weight does not exceed 100%.
 12. Theprocess according to claim 11, wherein the imine of the formula I isprepared in the presence of an acid or of a heterogeneous catalystselected from the group consisting of aluminum oxide, titanium dioxide,zirconium dioxide, silicon oxide and clay mineral, and mixtures thereof.13. The process according to claim 11, comprising preparing a chiralamine of formula VIII

where R¹, R² are each C₁-C₆-alkyl, C₃-C₆-cycloalkyl, C₂-C₆-alkenyl,C₁-C₆-alkynyl, C₂-C₆-haloalkenyl, C₂-C₆-haloalkynyl,C₁-C₆-alkoxycarbonyl, C₃-C₆-alkenyloxy-carbonyl,C₃-C₆-alkynyloxycarbonyl, aminocarbonyl, C₁-C₆-alkylaminocarbonyl,C₃-C₆-alkenylaminocarbonyl, C₃-C₆-alkynylamino-carbonyl,C₁-C₆-alkylsulfonylaminocarbonyl, di(C₁-C₆-alkyl)aminocarbonyl,N-(C₃-C₆-alkenyl)-N-(C₁-C₆-alkyl)aminocarbonyl,N-(C₃-C₆-alkynyl)-N-(C₁-C₆-alkyl)aminocarbonyl,N-(C₁-C₆-alkoxy)-N-(C₁-C₆-alkyl)aminocarbonyl,N-(C₃-C₆-alkenyl)-N-(C₁-C₆-alkoxy)aminocarbonyl,N-(C₃-C₆-alkynyl)-N-(C₁-C₆-alkoxy)aminocarbonyl,(C₁-C₆-alkyl)aminothiocarbonyl, di(C₁-C₆-alkyl)aminothiocarbonyl orC₁-C₆-alkylcarbonyl-C₁-C₆-alkyl, where the alkyl, cycloalkyl and alkoxyradicals mentioned are optionally partially or fully halogenated andoptionally have from one to three of: cyano, hydroxyl, C₁-C₄-alkyl,C₃-C₆-cycloalkyl, C₁-C₆-alkoxy-C₁-C₄-alkyl,C₁-C₄-alkoxy-C₁-C₄-alkoxy-C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-alkylthio,amino, C₁-C₄-alkylamino, di(C₁-C₄-alkyl)amino, C₁-C₄-alkylcarbonylamino,hydroxycarbonyl, C₁-C₄-alkoxycarbonyl, aminocarbonyl,C₁-C₄-alkylaminocarbonyl, di(C₁-C₄-alkyl)aminocarbonyl orC₁-C₄-alkylcarbonyloxy, aryl, aryl-C₁-C₄-alkyl, aryl-C₁-C₄-alkenyl,aryl-C₇-C₄-alkynyl, aryl-C₁-C₄-haloalkyl, aryl-C₇-C₄-haloalkenyl,aryl-C₃-C₄-haloalkynyl, aryl-C₁-C₄-hydroxyalkyl,arylcarbonyl-C₁-C₄-alkyl, aryl-C₁-C₄-alkylcarbonyl-C₁-C₄-alkyl,arylcarbonyloxy-C₁-C₄-alkyl, aryloxycarbonyl-C₁-C₄-alkyl,aryloxy-C₁-C₄-alkyl, arylamino-C₁-C₄-alkyl, arylthio-C₁-C₄-alkyl,arylsulfinyl-C₁-C₄-alkyl, arylsulfonyl-C₁-C₄-alkyl, heterocyclyl,heterocyclyl-C₁-C₄-alkyl, heterocyclyl-C₂-C₄-alkenyl,heterocyclyl-C₁-C₄-alkynyl, heterocyclyl-C₁-C₄-haloalkyl,heterocyclyl-C₇-C₄-haloalkenyl, heterocyclyl-C₃-C₄-haloalkynyl,heterocyclyl-C₁-C₄-hydroxyalkyl, heterocyclylcarbonyl-C₁-C₄-alkyl,heterocyclyl-C₁-C₄-alkyl-carbonyl-C₁-C₄-alkyl,heterocyclylcarbonyloxy-C₁-C₄-alkyl,heterocyclyloxycarbonyl-C₁-C₄-alkyl, heterocyclyloxy-C₁-C₄-alkyl,heterocyclylamino-C₁-C₄-alkyl, heterocyclylthio-C₁-C₄-alkyl,heterocyclylsulfinyl-C₁-C₄-alkyl, heterocyclylsulfonyl-C₁-C₄-alkyl,where the aforementioned radicals are optionally partially or fullyhalogenated and optionally have from one to three radicals from thegroup consisting of cyano, nitro, C₁-C₆-alkyl, C₁-C₆-haloalkyl,hydroxycarbonyl-C₁-C₆-alkyl, C₁-C₄-alkoxycarbonyl-C₁-C₆-alkyl, hydroxyl,C₁-C₆-hydroxyalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, hydroxycarbonyl,C₁-C₆-alkoxycarbonyl, aminocarbonyl, (C₁-C₆-alkyl)aminocarbonyl,di(C₁-C₆-alkyl)aminocarbonyl, hydroxycarbonyl-C₁-C₆-alkoxy,C₁-C₆-alkoxycarbonyl-C₁-C₆-alkoxy, amino, C₁-C₆-alkylamino,di(C₁-C₆-alkyl)amino, C₁-C₆-alkylsulfonylamino,C₁-C₆-haloalkyl-sulfonylamino, (C₁-C₆-alkyl)aminocarbonylamino,di(C₁-C₆-alkyl)-aminocarbonylamino, aryl and aryl(C₁-C₆-alkyl); wherethe R¹ and R² radicals are different than one another; comprising: a)reacting a ketone of the formula III with an amine of the formula IV toprepare the amine according to formula I where R³ is C₁-C₆-alkyl; R⁴ isaryl which is optionally partially or fully halogenated and optionallyhave from one to three radicals from the group consisting of cyano,nitro, C₁-C₆-alkyl, C₁-C₆-haloalkyl, hydroxyl, C₁-C₆-hydroxyalkyl,C₁-C₆-alkoxy, C₁-C₆-haloalkoxy, hydroxycarbonyl, C₁-C₆-alkoxy-carbonyl,C₁-C₆-alkylamino, di(C₁-C₆-alkyl)amino, aryl and aryl(C₁-C₆-alkyl); b)reacting the imine of the formula I obtained from a) with hydrogen and aheterogeneous copper-containing catalyst, where the heterogeneouscopper-containing catalyst comprises, based on the total weight of thecatalyst, 0.1-95% by weight of copper, 0.1-85% by weight of at least onemetal selected from the group of nickel, cobalt and zinc; 0-15% byweight of at least one promoter selected from the group of iron,rhodium, ruthenium, palladium, platinum, iridium, osmium, silver, gold,molybdenum, tungsten, rhenium, cadmium, lead, manganese, tin, chromium,lithium, sodium, potassium, cesium, magnesium, barium, phosphorus,arsenic, antimony, bismuth, selenium and tellurium; where the sum of thepercentages by weight does not exceed 100%; c) subsequentlyhydrogenolytically cleaving the amine of the formula II obtained fromstep b).
 14. The process according to claim 13, wherein thehydrogenolysis is carried out by hydrogen in the presence of aheterogeneous catalyst selected from the group consisting of theplatinum metal elements.
 15. The process according to claim 14, whereinthe hydrogenolysis is carried out with metal hydrides or mixtures ofmetal hydrides.
 16. The process according to claim 1, wherein theprocess is carried out continuously, semicontinuously or batchwise. 17.The process according to claim 1, where a parent amine of the chiralimine is chiral and a parent ketone of the chiral imine is prochiral,with hydrogen.